Tumor suppressors represent a critical line of defense against tumorigenesis. Their mechanisms of action and the pathways they are involved in provide important insights into cancer progression, vulnerabilities, and treatment options. Although nuclear and cytosolic tumor suppressors have been extensively investigated, relatively little is known about tumor suppressors localized within the mitochondria. However, recent research has begun to uncover the roles of these important proteins in suppressing tumorigenesis. Here, we review this newly developing field and summarize available information on mitochondrial tumor suppressors.

Department of Cell Biology Faculty of Science Charles University Prague Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Prague Czech Republic

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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424. PubMed

Hofmarcher T, Lindgren P, Wilking N, Jönsson B. The cost of cancer in Europe 2018. Eur J Cancer 2020;129:41–9. PubMed

Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 1971;68:820–3. PubMed PMC

Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, et al. . A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986;323:643–6. PubMed

Dryja TP, Friend S, Weinberg RA. Genetic sequences that predispose to retinoblastoma and osteosarcoma. Symp Fundam Cancer Res 1986;39:115–9. PubMed

Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81:323–30. PubMed

Linzer DI, Levine AJ. Characterization of a 54K Dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 1979;17:43–52. PubMed

Lane DP, Crawford LV. T antigen is bound to a host protein in SV40-transformed cells. Nature 1979;278:261–3. PubMed

Kress M, May E, Cassingena R, May P. Simian virus 40-transformed cells express new species of proteins precipitable by anti-simian virus 40 tumor serum. J Virol 1979;31:472–83. PubMed PMC

Finlay CA, Hinds PW, Levine AJ. The p53 proto-oncogene can act as a suppressor of transformation. Cell 1989;57:1083–93. PubMed

Levine AJ, Finlay CA, Hinds PW. P53 is a tumor suppressor gene. Cell 2004;116:S67–9. PubMed

Peitsaro N, Polianskyte Z, Tuimala J, Porn-Ares I, Liobikas J, Speer O, et al. . Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy. BMC Evol Biol 2008;8:26. PubMed PMC

Smith TS, Southan C, Ellington K, Campbell D, Tew DG, Debouck C. Identification, genomic organization, and mRNA expression of LACTB, encoding a serine beta-lactamase-like protein with an amino-terminal transmembrane domain. Genomics 2001;78:12–4. PubMed

Keckesova Z, Donaher JL, De Cock J, Freinkman E, Lingrell S, Bachovchin DA, et al. . LACTB is a tumor suppressor that modulates lipid metabolism and cell state. Nature 2017;543:681–6. PubMed PMC

Polianskyte Z, Peitsaro N, Dapkunas A, Liobikas J, Soliymani R, Lalowski M, et al. . LACTB is a filament-forming protein localized in mitochondria. Proc Natl Acad Sci U S A 2009;106:18960–95. PubMed PMC

Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, et al. . A mitochondrial protein compendium elucidates complex I disease biology. Cell 2008;134:112–23. PubMed PMC

Koc EC, Burkhart W, Blackburn K, Moyer MB, Schlatzer DM, Moseley A, et al. . The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present. J Biol Chem 2001;276:43958–69. PubMed

Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, et al. . Variations in DNA elucidate molecular networks that cause disease. Nature 2008;452:429–35. PubMed PMC

Yang X, Deignan JL, Qi H, Zhu J, Qian S, Zhong J, et al. . Validation of candidate causal genes for obesity that affect shared metabolic pathways and networks. Nat Genet 2009;41:415–23. PubMed PMC

Lu JB, Yao X, Xiu J, Y H. MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages. Arch Biochem Biophys 2016;590:64–71. PubMed

Zhang J, He Y, Yu Y, Chen X, Cui G, Wang W, et al. . Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. Cancer Med 2018;7:3351–62. PubMed PMC

Li HT, Dong DY, Liu Q, Xu YQ, Chen L. Overexpression of LACTB, a mitochondrial protein that inhibits proliferation and invasion in glioma cells. Oncol Res 2019;27:423–9. PubMed PMC

Xu W, Yu M, Qin J, Luo Y, Zhong M. LACTB regulates PIK3R3 to promote autophagy and inhibit EMT and proliferation through the PI3K/AKT/mTOR signaling pathway in colorectal cancer. Cancer Manag Res 2020;12:5181–200. PubMed PMC

Xue C, He Y, Zhu W, Chen X, Yu Y, Hu Q, et al. . Low expression of LACTB promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma. Am J Transl Res 2018;10:4152–62. PubMed PMC

Zeng K, Chen X, Hu X, Liu X, Xu T, Sun H, et al. . LACTB, a novel epigenetic silenced tumor suppressor, inhibits colorectal cancer progression by attenuating MDM2-mediated p53 ubiquitination and degradation. Oncogene 2018;37:5534–51. PubMed

Ma Y, Wang L, He F, Yang J, Ding Y, Ge S, et al. . LACTB suppresses melanoma progression by attenuating PP1A and YAP interaction. Cancer Lett 2021;506:67–82. PubMed

Du J, Zhang P, Zhao X, He J, Xu Y, Zou Q, et al. . MicroRNA-351-5p mediates skeletal myogenesis by directly targeting lactamase-beta and is regulated by lnc-mg. FASEB J 2019;33:1911–26. PubMed

Yang X, Zhang D, Liu S, Li X, Hu W, Han C. KLF4 suppresses the migration of hepatocellular carcinoma by transcriptionally upregulating monoglyceride lipase. Am J Cancer Res 2018;8:1019–29. PubMed PMC

Xie J, Peng Y, Chen X, Li Q, Jian B, Wen Z, et al. . LACTB mRNA expression is increased in pancreatic adenocarcinoma and high expression indicates a poor prognosis. PLoS One 2021;16:e0245908. PubMed PMC

Peng LX, Wang MD, Xie P, Yang JP, Sun R, Zheng LS, et al. . LACTB promotes metastasis of nasopharyngeal carcinoma via activation of ERBB3/EGFR-ERK signaling resulting in unfavorable patient survival. Cancer Lett 2021;498:165–77. PubMed

Hancock CN, Liu W, Alvord WG, Phang JM. Co-regulation of mitochondrial respiration by proline dehydrogenase/oxidase and succinate. Amino Acids 2016;48:859–72. PubMed PMC

Polyak K, Xia Y, Zweier JL, Kinzler KW, Vogelstein B. A model for p53-induced apoptosis. Nature 1997;389:300–5. PubMed

Raimondi I, Ciribilli Y, Monti P, Bisio A, Pollegioni L, Fronza G, et al. . P53 family members modulate the expression of PRODH, but not PRODH2, via intronic p53 response elements. PLoS One 2013;8:e69152. PubMed PMC

Maxwell SA, Kochevar GJ. Identification of a p53-response element in the promoter of the proline oxidase gene. Biochem Biophys Res Commun 2008;369:308–13. PubMed

Liu Y, Borchert GL, Donald SP, Diwan BA, Anver M, Phang JM. Proline oxidase functions as a mitochondrial tumor suppressor in human cancers. Cancer Res 2009;69:6414–22. PubMed PMC

Liu W, Zabirnyk O, Wang H, Shiao YH, Nickerson ML, Khalil S, et al. . miR-23b targets proline oxidase, a novel tumor suppressor protein in renal cancer. Oncogene 2010;29:4914–24. PubMed PMC

Liu W, Le A, Hancock C, Lane AN, Dang CV, Fan TW, et al. . Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC. Proc Natl Acad Sci U S A 2012;109:8983–8. PubMed PMC

Maxwell SA, Davis GE. Differential gene expression in p53-mediated apoptosis-resistant vs. apoptosis-sensitive tumor cell lines. Proc Natl Acad Sci U S A 2000;97:13009–14. PubMed PMC

Maxwell SA, Rivera A. Proline oxidase induces apoptosis in tumor cells, and its expression is frequently absent or reduced in renal carcinomas. J Biol Chem 2003;278:9784–9. PubMed

Hu CA, Donald SP, Yu J, Lin WW, Liu Z, Steel G, et al. . Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. Mol Cell Biochem 2007;295:85–92. PubMed

Donald SP, Sun XY, Hu CA, Yu J, Mei JM, Valle D, et al. . Proline oxidase, encoded by p53-induced gene-6, catalyzes the generation of proline-dependent reactive oxygen species. Cancer Res 2001;61:1810–5. PubMed

Liu Y, Borchert GL, Surazynski A, Phang JM. Proline oxidase, a p53-induced gene, targets COX-2/PGE2 signaling to induce apoptosis and inhibit tumor growth in colorectal cancers. Oncogene 2008;27:6729–37. PubMed PMC

Liu Y, Borchert GL, Donald SP, Surazynski A, Hu CA, Weydert CJ, et al. . MnSOD inhibits proline oxidase-induced apoptosis in colorectal cancer cells. Carcinogenesis 2005;26:1335–42. PubMed

Rivera A, Maxwell SA. The p53-induced gene-6 (proline oxidase) mediates apoptosis through a calcineurin-dependent pathway. J Biol Chem 2005;280:29346–54. PubMed

Liu Y, Borchert GL, Surazynski A, Hu CA, Phang JM. Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis: the role of ROS/superoxides, NFAT and MEK/ERK signaling. Oncogene 2006;25:5640–7. PubMed

Pandhare J, Cooper SK, Phang JM. Proline oxidase, a proapoptotic gene, is induced by troglitazone: evidence for both peroxisome proliferator-activated receptor gamma-dependent and -independent mechanisms. J Biol Chem 2006;281:2044–52. PubMed

Kim KY, Ahn JH, Cheon HG. Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation. Mol Pharmacol 2007;72:674–85. PubMed

Wang J, Lv X, Shi J, Hu X, Du Y. Troglitazone induced apoptosis via PPARγ activated POX-induced ROS formation in HT29 cells. Biomed Environ Sci 2011;24:391–9. PubMed

Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology 1994;107:1183–8. PubMed

Nagano T, Nakashima A, Onishi K, Kawai K, Awai Y, Kinugasa M, et al. . Proline dehydrogenase promotes senescence through the generation of reactive oxygen species. J Cell Sci 2017;130:1413–20. PubMed

Liu W, Glunde K, Bhujwalla ZM, Raman V, Sharma A, Phang JM. Proline oxidase promotes tumor cell survival in hypoxic tumor microenvironments. Cancer Res 2012;72:3677–86. PubMed PMC

Pandhare J, Donald SP, Cooper SK, Phang JM. Regulation and function of proline oxidase under nutrient stress. J Cell Biochem 2009;107:759–68. PubMed PMC

Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T, Borge L, et al. . Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nat Commun 2017;8:16031. PubMed PMC

Liu Y, Mao C, Wang M, Liu N, Ouyang L, Liu S, et al. . Cancer progression is mediated by proline catabolism in non-small cell lung cancer. Oncogene 2020;39:2358–76. PubMed

Dik E, Naamati A, Asraf H, Lehming N, Pines O. Human fumarate hydratase is dual localized by an alternative transcription initiation mechanism. Traffic 2016;17:720–32. PubMed

Yogev O, Naamati A, Pines O. Fumarase: a paradigm of dual targeting and dual localized functions. FEBS J 2011;278:4230–42. PubMed

Castro-Vega LJ, Buffet A, De Cubas AA, Cascón A, Menara M, Khalifa E, et al. . Germline mutations in FH confer predisposition to malignant pheochromocytomas and paragangliomas. Hum Mol Genet 2014;23:2440–6. PubMed

Clark GR, Sciacovelli M, Gaude E, Walsh DM, Kirby G, Simpson MA, et al. . Germline FH mutations presenting with pheochromocytoma. J Clin Endocrinol Metab 2014;99:E2046–50. PubMed

Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, et al. . Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Nat Genet 2002;30:406–10. PubMed

Alam NA, Olpin S, Rowan A, Kelsell D, Leigh IM, Tomlinson IP, et al. . Missense mutations in fumarate hydratase in multiple cutaneous and uterine leiomyomatosis and renal cell cancer. J Mol Diagn 2005;7:437–43. PubMed PMC

Schmidt C, Sciacovelli M, Frezza C. Fumarate hydratase in cancer: a multifaceted tumor suppressor. Semin Cell Dev Biol 2020;98:15–25. PubMed PMC

Alderson NL, Wang Y, Blatnik M, Frizzell N, Walla MD, Lyons TJ, et al. . S-(2 -Succinyl)cysteine: a novel chemical modification of tissue proteins by a Krebs cycle intermediate. Arch Biochem Biophys 2006;450:1–8. PubMed

Blatnik M, Frizzell N, Thorpe SR, Baynes JW. Inactivation of glyceraldehyde-3-phosphate dehydrogenase by fumarate in diabetes. Diabetes 2008;57:41. PubMed PMC

Ternette N, Yang M, Laroyia M, Kitagawa M, O'Flaherty L, Wolhulter K, et al. . Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency. Cell Rep 2013;3:689–700. PubMed PMC

Kerins MA-O, Vashisht AA, Liang BX, Duckworth SJ, Praslicka BJ, Wohlschlegel JA, et al. . Fumarate mediates a chronic proliferative signal in fumarate hydratase-inactivated cancer cells by increasing transcription and translation of ferritin genes. Mol Cell Biol 2017;37:e00079–17. PubMed PMC

Adam J, Hatipoglu E, O'Flaherty L, Ternette N, Sahgal N, Lockstone H, et al. . Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell 2011;20:524–37. PubMed PMC

Bardella C, El-Bahrawy M, Frizzell N, Adam J, Ternette N, Hatipoglu E, et al. . Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status. J Pathol 2011;225:4–11. PubMed

Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia 2015;3:83–92. PubMed PMC

Isaacs JS, Jung YJ, Mole DR, Lee S, Torres-Cabala C, Chung YL, et al. . HIF overexpression correlates with biallelic loss of fumarate hydratase in renal cancer: novel role of fumarate in regulation of HIF stability. Cancer Cell 2005;8:143–53. PubMed

Bardella C, Olivero M, Lorenzato A, Geuna M, Adam J, O'Flaherty L, et al. . Cells lacking the fumarase tumor suppressor are protected from apoptosis through a hypoxia-inducible factor-independent, AMPK-dependent mechanism. Mol Cell Biol 2012;32:3081–94. PubMed PMC

Pollard P, Wortham N, Barclay E, Alam A, Elia G, Manek S, et al. . Evidence of increased microvessel density and activation of the hypoxia pathway in tumors from the hereditary leiomyomatosis and renal cell cancer syndrome. J Pathol 2005;205:41–9. PubMed

Costa B, Dettori D, Lorenzato A, Bardella C, Coltella N, Martino C, et al. . Fumarase tumor suppressor gene and MET oncogene cooperate in upholding transformation and tumorigenesis. FASEB J 2010;24:2680–8. PubMed

Pollard PJ, Brière JJ, Alam NA, Barwell J, Barclay E, Wortham NC, et al. . Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumors which result from germline FH and SDH mutations. Hum Mol Genet 2005;14:2231–9. PubMed

Sudarshan S, Sourbier C, Kong HS, Block K, V Romero VA, Yang Y, et al. . Fumarate hydratase deficiency in renal cancer induces glycolytic addiction and hypoxia-inducible transcription factor 1alpha stabilization by glucose-dependent generation of reactive oxygen species. Mol Cell Biol 2009;29:4080–90. PubMed PMC

Tong WH, Sourbier C, Kovtunovych G, Jeong SY, Vira M, Ghosh M, et al. . The glycolytic shift in fumarate-hydratase-deficient kidney cancer lowers AMPK levels, increases anabolic propensities and lowers cellular iron levels. Cancer Cell 2011;20:315–27. PubMed PMC

Tyrakis PA, Yurkovich ME, Sciacovelli M, Papachristou EK, Bridges HR, Gaude E, et al. . Fumarate hydratase loss causes combined respiratory chain defects. Cell Rep 2017;21:1036–47. PubMed PMC

Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, et al. . Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev 2012;26:1326–38. PubMed PMC

Sciacovelli M, Gonçalves E, Johnson TI, Zecchini VR, da Costa AS, Gaude E, et al. . Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature 2016;537:544–7. PubMed PMC

He X, Yan B, Liu S, Jia J, Lai W, Xin X, et al. . Chromatin remodeling factor LSH drives cancer progression by suppressing the activity of fumarate hydratase. Cancer Res 2016;76:5743–55. PubMed PMC

Jiang Y, Qian X, Shen J, Wang Y, Li X, Liu R, et al. . Local generation of fumarate promotes DNA repair through inhibition of histone H3 demethylation. Nat Cell Biol 2015;17:1158–68. PubMed PMC

Yogev O, Yogev O, Singer E, Shaulian E, Goldberg M, Fox TD, et al. . Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response. PLoS Biol 2010;8:e1000328. PubMed PMC

Leshets M, Ramamurthy D, Lisby M, Lehming N, Pines O. Fumarase is involved in DNA double-strand break resection through a functional interaction with Sae2. Curr Genet 2018;64:697–712. PubMed

Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, et al. . Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nat Genet 2018;50:1086–92. PubMed PMC

Johnson TI, Costa ASH, Ferguson AN, Frezza C. Fumarate hydratase loss promotes mitotic entry in the presence of DNA damage after ionising radiation. Cell Death Dis 2018;9:913. PubMed PMC

Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, Whitten D, et al. . An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma. Cancer Cell 2011;20:511–23. PubMed

Zheng L, Cardaci S, Jerby L, MacKenzie ED, Sciacovelli M, Johnson TI, et al. . Fumarate induces redox-dependent senescence by modifying glutathione metabolism. Nat Commun 2015;6:6001. PubMed PMC

Sourbier C, Ricketts CJ, Matsumoto S, Crooks DR, Liao PJ, Mannes PZ, et al. . Targeting ABL1-mediated oxidative stress adaptation in fumarate hydratase-deficient cancer. Cancer Cell 2014;26:840–50. PubMed PMC

Gonçalves E, Sciacovelli M, Costa ASH, Tran MGB, Johnson TI, Machado D, et al. . Post-translational regulation of metabolism in fumarate hydratase deficient cancer cells. Metab Eng 2018;45:149–57. PubMed PMC

Yang Y, Lane AN, Ricketts CJ, Sourbier C, Wei MH, Shuch B, et al. . Metabolic reprogramming for producing energy and reducing power in fumarate hydratase null cells from hereditary leiomyomatosis renal cell carcinoma. PLoS One 2013;8:e72179. PubMed PMC

Mullen AR, Wheaton WW, Jin ES, Chen PH, Sullivan LB, Cheng T, et al. . Reductive carboxylation supports growth in tumor cells with defective mitochondria. Nature 2011;481:385–8. PubMed PMC

Garcia D, Shaw RJ. AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell 2017;66:789–800. PubMed PMC

Boettcher M, Lawson A, Ladenburger V, Fredebohm J, Wolf J, Hoheisel JD, et al. . High throughput synthetic lethality screen reveals a tumorigenic role of adenylate cyclase in fumarate hydratase-deficient cancer cells. BMC Genomics 2014;15:158. PubMed PMC

Yu HE, Wang F, Yu F, Zeng ZL, Wang Y, Lu YX, et al. . Suppression of fumarate hydratase activity increases the efficacy of cisplatin-mediated chemotherapy in gastric cancer. Cell Death Dis 2019;10:413. PubMed PMC

Leshets M, Silas YBH, Lehming N, Pines O. Fumarase: From the TCA Cycle to DNA damage response and tumor suppression. Front Mol Biosci 2018;5:68. PubMed PMC

Yang M, Soga T, Pollard PJ, Adam J. The emerging role of fumarate as an oncometabolite. Front Oncol 2012;2:85. PubMed PMC

Ye X, Li M, Hou T, Gao T, Zhu WG, Yang Y. Sirtuins in glucose and lipid metabolism. Oncotarget 2017;8:1845–59. PubMed PMC

George J, Ahmad N. Mitochondrial sirtuins in cancer: emerging roles and therapeutic potential. Cancer Res 2016;76:2500–6. PubMed PMC

Singh CK, Chhabra G, Ndiaye MA, Garcia-Peterson LM, Mack NJ, Ahmad N. The role of sirtuins in antioxidant and redox signaling. Antioxid Redox Signal 2018;28:643–61. PubMed PMC

Du Y, Hu H, Hua C, Du K, Wei T. Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms. Biochem Biophys Res Commun 2018;503:763–9. PubMed

Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 2005;16:4623–35. PubMed PMC

Schwer B, North BJ, Frye RA, Ott M, Verdin E. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase. J Cell Biol 2002;158:647–57. PubMed PMC

Scher MB, Vaquero A, Reinberg D. SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress. Genes Dev 2007;21:920–8. PubMed PMC

Frye RA. Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem Biophys Res Commun 1999;260:273–9. PubMed

Tanner KG, Landry J, Sternglanz R, Denu JM. Silent information regulator 2 family of NAD- dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. Proc Natl Acad Sci U S A 2000;97:14178–82. PubMed PMC

Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 2000;403:795–800. PubMed

Du J, Zhou Y, Su X, Yu JJ, Khan S, Jiang H, et al. . Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 2011;334:806–9. PubMed PMC

Yu W, Denu RA, Krautkramer KA, Grindle KM, Yang DT, Asimakopoulos F, et al. . Loss of SIRT3 provides growth advantage for B cell malignancies. J Biol Chem 2016;291:3268–79. PubMed PMC

Zhang YY, Zhou LM. Sirt3 inhibits hepatocellular carcinoma cell growth through reducing Mdm2-mediated p53 degradation. Biochem Biophys Res Commun 2012;423:26–31. PubMed

Xu WY, Hu QS, Qin Y, Zhang B, Liu WS, Ni QX, et al. . Zinc finger E-box-binding homeobox 1 mediates aerobic glycolysis via suppression of sirtuin 3 in pancreatic cancer. World J Gastroenterol 2018;24:4893–905. PubMed PMC

Xiao K, Jiang J, Wang W, Cao S, Zhu L, Zeng H, et al. . Sirt3 is a tumor suppressor in lung adenocarcinoma cells. Oncol Rep 2013;30:1323–8. PubMed

Wang L, Wang WY, Cao LP. SIRT3 inhibits cell proliferation in human gastric cancer through down-regulation of Notch-1. Int J Clin Exp Med 2015;8:5263–71. PubMed PMC

Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, et al. . SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell 2010;17:41–52. PubMed PMC

Finley LWS, Carracedo A, Lee J, Souza A, Egia A, Zhang J, et al. . SIRT3 opposes reprogramming of cancer cell metabolism through HIF1α destabilization. Cancer Cell 2011;19:416–28. PubMed PMC

Bell EL, Emerling BM, Ricoult SJ, Guarente L. SirT3 suppresses hypoxia inducible factor 1α and tumor growth by inhibiting mitochondrial ROS production. Oncogene 2011;30:2986–96. PubMed PMC

Krebs AM, Mitschke J, Lasierra LM, Schmalhofer O, Boerries M, Busch H, et al. . The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol 2017;19:518–29. PubMed

Marfe G, Tafani M, Indelicato M, Sinibaldi-Salimei P, Reali V, Pucci B, et al. . Kaempferol induces apoptosis in two different cell lines via Akt inactivation, Bax and SIRT3 activation, and mitochondrial dysfunction. J Cell Biochem 2009;106:643–50. PubMed

Dhanasekaran DN, Reddy EP. JNK signaling in apoptosis. Oncogene 2008;27:6245–51. PubMed PMC

Winter JN, Jefferson LS, Kimball SR. ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling. Am J Physiol Cell Physiol 2011;300:C1172–80. PubMed PMC

Alhazzazi TY, Kamarajan P, Joo N, Huang JY, Verdin E, D'Silva NJ, et al. . Sirtuin-3 (SIRT3), a novel potential therapeutic target for oral cancer. Cancer 2011;117:1670–8. PubMed PMC

Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CF, Steegborn C. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol 2008;382:790–801. PubMed

Kamarajan P, Alhazzazi TY, Danciu T, D'Silva NJ, Verdin E, Kapila YL. Receptor-interacting protein (RIP) and Sirtuin-3 (SIRT3) are on opposite sides of anoikis and tumorigenesis. Cancer 2012;118:5800–10. PubMed PMC

George J, Nihal M, Singh CK, Zhong W, Liu X, Ahmad N. Pro-proliferative function of mitochondrial sirtuin deacetylase SIRT3 in human melanoma. J Invest Dermatol 2016;136:809–18. PubMed PMC

Choi J, Koh E, Lee YS, Lee HW, Kang HG, Yoon YE, et al. . Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma. Biochem Biophys Res Commun 2016;474:547–53. PubMed

Li S, Banck M, Mujtaba S, Zhou MM, Sugrue MM, Walsh MJ. p53-induced growth arrest is regulated by the mitochondrial SirT3 deacetylase. PLoS One 2010;5:e10486. PubMed PMC

Ahuja N, Schwer B, Carobbio S, Waltregny D, North BJ, Castronovo V, et al. . Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase. J Biol Chem 2007;282:33583–92. PubMed

Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJJ, et al. . SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells. Cell 2006;126:941–54. PubMed

Argmann C, Auwerx J. Insulin secretion: SIRT4 gets in on the act. Cell 2006;126:837–9. PubMed

Laurent G, German NJ, Saha AK, de Boer VCJ, Davies M, Koves TR, et al. . SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell 2013;50:686–98. PubMed PMC

Anderson KA, Huynh FK, Fisher-Wellman K, Stuart JD, Peterson BS, Douros JD, et al. . SIRT4 is a lysine deacylase that controls leucine metabolism and insulin secretion. Cell Metab 2017;25:838–55. PubMed PMC

Huang G, Lai X, Chen Z, Yu Z, Zhou D, Wang P, et al. . Sirtuin-4 (SIRT4) is downregulated in hepatocellular carcinoma and associated with clinical stage. Int J Clin Exp Pathol 2016;9:6511–7.

Huang G, Cheng J, Yu F, Liu X, Yuan C, Liu C, et al. . Clinical and therapeutic significance of sirtuin-4 expression in colorectal cancer. Oncol Rep 2016;35:2801–10. PubMed

Sun H, Huang D, Liu G, Jian F, Zhu J, Zhang L. SIRT4 acts as a tumor suppressor in gastric cancer by inhibiting cell proliferation, migration, and invasion. Onco Targets Ther 2018;11:3959–68. PubMed PMC

Fu L, Dong Q, He J, Wang X, Xing J, Wang E, et al. . SIRT4 inhibits malignancy progression of NSCLCs, through mitochondrial dynamics mediated by the ERK-Drp1 pathway. Oncogene 2017;36:2724–36. PubMed

Huang G, Cui F, Yu F, Lu H, Zhang M, Tang H, et al. . Sirtuin-4 (SIRT4) is downregulated and associated with some clinicopathological features in gastric adenocarcinoma. Biomed Pharmacother 2015;72:135–9. PubMed

Jeong SM, Xiao C, Finley LW, Lahusen T, Souza AL, Pierce K, et al. . SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell 2013;23:450–63. PubMed PMC

Mathias RA, Greco TM, Oberstein A, Budayeva HG, Chakrabarti R, Rowland EA, et al. . Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 2014;159:1615–25. PubMed PMC

Perham RN. Domains, motifs, and linkers in 2-oxo acid dehydrogenase multienzyme complexes: a paradigm in the design of a multifunctional protein. Biochemistry 1991;30:8501–12. PubMed

Miyo M, Yamamoto H, Konno M, Colvin H, Nishida N, Koseki J, et al. . Tumor-suppressive function of SIRT4 in human colorectal cancer. Br J Cancer 2015;113:492–9. PubMed PMC

Lai X, Yu Z, Chen X, Huang G. SIRT4 is upregulated in Chinese patients with esophageal cancer. Int J Clin Exp Pathol 2016;9:10543–9.

Huang G, Lin Y, Zhu G. SIRT4 is upregulated in breast cancer and promotes the proliferation, migration and invasion of breast cancer cells. Int J Clin Exp Pathol 2017;10:11849–56. PubMed PMC

Jeong SM, Hwang S, Seong RH. SIRT4 regulates cancer cell survival and growth after stress. Biochem Biophys Res Commun 2016;470:251–6. PubMed

Uzhachenko R, Ivanov SV, Yarbrough WG, Shanker A, Medzhitov R, Ivanova AV. Fus1/Tusc2 is a novel regulator of mitochondrial calcium handling, Ca2+-coupled mitochondrial processes, and Ca2+-dependent NFAT and NF-κB pathways in CD4+ T cells. Antioxid Redox Signal 2014;20:1533–47. PubMed PMC

Lerman MI, Minna JD. The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. Cancer Res 2000;60:6116–33. PubMed

Prudkin L, Behrens C, Liu DD, Zhou X, Ozburn NC, Bekele BN, et al. . Loss and reduction of FUS1 protein expression is a frequent phenomenon in the pathogenesis of lung cancer. Clin Cancer Res 2008;14:41–7. PubMed PMC

Liang S, Zhang N, Deng Y, Chen L, Zhang Y, Zheng Z, et al. . miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2. Exp Ther Med 2017;14:1095–103. PubMed PMC

Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L, et al. . miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Mol Cancer Res 2009;7:1234–43. PubMed PMC

Lin J, Xu K, Gitanjali J, Roth JA, Ji L. Regulation of tumor suppressor gene FUS1 expression by the untranslated regions of mRNA in human lung cancer cells. Biochem Biophys Res Commun 2011;410:235–41. PubMed PMC

Kondo M, Ji L, Kamibayashi C, Tomizawa Y, Randle D, Sekido Y, et al. . Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung cancer cells. Oncogene 2001;20:6258–62. PubMed

Ji L, Roth JA. Tumor suppressor FUS1 signaling pathway. J Thorac Oncol 2008;3:327–30. PubMed PMC

Deng WG, Kawashima H, Wu G, Jayachandran G, Xu K, Minna JD, et al. . Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with down-regulation of murine double minute-2 and activation of the apoptotic protease-activating factor 1-dependent apoptotic pathway in human non-small cell lung cancer cells. Cancer Res 2007;67:709–17. PubMed

Lin J, Sun T, Ji L, Deng W, Roth J, Minna J, et al. . Oncogenic activation of c-Abl in non-small cell lung cancer cells lacking FUS1 expression: inhibition of c-Abl by the tumor suppressor gene product Fus1. Oncogene 2007;26:6989–96. PubMed PMC

Meng J, Majidi M, Fang B, Ji L, Bekele BN, Minna JD, et al. . The tumor suppressor gene TUSC2 (FUS1) sensitizes NSCLC to the AKT inhibitor MK2206 in LKB1-dependent manner. PLoS One 2013;8:e77067. PubMed PMC

Shah U, Sharpless NE, Hayes DN. LKB1 and lung cancer: more than the usual suspects. Cancer Res 2008;68:3562–5. PubMed

Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: metabolism and growth control in tumor suppression. Nat Rev Cancer 2009;9:563–75. PubMed PMC

Uzhachenko R, Issaeva N, Boyd K, Ivanov SV, Carbone DP, Ivanova AV. Tumor suppressor Fus1 provides a molecular link between inflammatory response and mitochondrial homeostasis. J Pathol 2012;227:456–69. PubMed

Rustin P, Munnich A, Rötig A. Succinate dehydrogenase and human diseases: new insights into a well-known enzyme. Eur J Hum Genet 2002;10:289–91. PubMed

Rutter J, Winge DR, Schiffman JD. Succinate dehydrogenase - Assembly, regulation and role in human disease. Mitochondrion 2010;10:393–401. PubMed PMC

Farshbaf MJ. Succinate dehydrogenase in Parkinson's disease. Front Biol 2017;12:175–82.

Bayley JP, Devilee P, Taschner PE. The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet 2005;6:39. PubMed PMC

Gimenez-Roqueplo A, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, et al. . Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res 2003;63:5615–21. PubMed

Kim S, Kim DH, Jung WH, Koo JS. Succinate dehydrogenase expression in breast cancer. Springerplus 2013;2:299. PubMed PMC

Apuria P, Lunt S, Väremo L, Vergnes L, Gozo M, Beach J, et al. . Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism. Cancer Metab 2014;2:21. PubMed PMC

Ishii T, Yasuda K, Akatsuka A, Hino O, Hartman PS, Ishii N. A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis. Cancer Res 2005;65:203–9. PubMed

Selak MA, Armour SM, MacKenzie ED, Boulahbel H, Watson DG, Mansfield KD, et al. . Succinate links TCA cycle dysfunction to oncogenesis by inhibiting HIF-alpha prolyl hydroxylase. Cancer Cell 2005;7:77–85. PubMed

Wagner AJ, Remillard SP, Zhang YX, Doyle LA, George S, Hornick JL. Loss of expression of SDHA predicts SDHA mutations in gastrointestinal stromal tumors. Mod Pathol 2013;26:289–94. PubMed

Astuti D, Morris M, Krona C, Abel F, Gentle D, Martinsson T, et al. . Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma. Br J Cancer 2004;91:1835–41. PubMed PMC

Wang H, Chen Y, Wu G. SDHB deficiency promotes TGFbeta-mediated invasion and metastasis of colorectal cancer through transcriptional repression complex SNAIL1-SMAD3/4. Transl Oncol 2016;9:512–20. PubMed PMC

Loriot C, Burnichon N, Gadessaud N, Vescovo L, Amar L, Libe R, et al. . Epithelial to mesenchymal transition is activated in metastatic pheochromocytomas and paragangliomas caused by SDHB gene mutations. J Clin Endocrinol Metab 2012;97:E954–62. PubMed

Killian JK, Miettinen M, Walker R, Wang Y, Zhu YJ, Waterfall1 JJ, et al. . Recurrent epimutation of SDHC in gastrointestinal stromal tumors. Sci Transl Med 2014;24:268ra177. PubMed PMC

Rosland GV, Dyrstad SE, Tusubira D, Helwa R, Tan TZ, Lotsberg ML, et al. . Epithelial to mesenchymal transition (EMT) is associated with attenuation of succinate dehydrogenase (SDH) in breast cancer through reduced expression of SDHC. Cancer Metab 2019;7:6. PubMed PMC

Baysal BE, Ferrell RE, Willett-Brozick JE, Lawrence EC, Myssiorek D, et al. . Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma. Science 2000;287:848–51. PubMed

Yu W, Ni Y, Saji M, Ringel MD, Jaini R, Eng C. Cowden syndrome-associated germline succinate dehydrogenase complex subunit D (SDHD) variants cause PTEN-mediated down-regulation of autophagy in thyroid cancer cells. Hum Mol Genet 2017;26:1365–75. PubMed PMC

Populo H, Batista R, Sampaio C, Pardal J, Lopes JM, Soares P. SDHD promoter mutations are rare events in cutaneous melanomas but SDHD protein expression is downregulated in advanced cutaneous melanoma. PLoS One 2017;12:e0180392. PubMed PMC

Zhang T, Xu M, Makowski MM, Lee C, Kovacs M, Fang J, et al. . SDHD promoter mutations ablate GABP transcription factor binding in melanoma. Cancer Res 2017;77:1649–61. PubMed PMC

Seibold S, Rudroff C, Weber M, Galle J, Wanner C, Marx M. Identification of a new tumor suppressor gene located at chromosome 8p21.3–22. FASEB J 2003;17:1180–2. PubMed

Bozgeyik I, Yumrutas O, Bozgeyik E. MTUS1, a gene encoding angiotensin-II type 2 (AT2) receptor-interacting proteins, in health and disease, with special emphasis on its role in carcinogenesis. Gene 2017;626:54–63. PubMed

Di Benedetto M, Pineau P, Nouet S, Berhouet S, Seitz I, Louis S, et al. . Mutation analysis of the 8p22 candidate tumor suppressor gene ATIP/MTUS1 in hepatocellular carcinoma. Mol Cell Endocrinol 2006;252:207–15. PubMed

Wang Y, Huang Y, Liu Y, Li J, Hao Y, Yin P, et al. . Microtubule associated tumor suppressor 1 interacts with mitofusins to regulate mitochondrial morphology in endothelial cells. FASEB J 2018;32:4504–18. PubMed

Di Benedetto M, Bièche I, Deshayes F, Vacher S, Nouet S, Collura V, et al. . Structural organization and expression of human MTUS1, a candidate 8p22 tumor suppressor gene encoding a family of angiotensin II AT2 receptor-interacting proteins, ATIP. Gene 2006;380:127–36. PubMed

Wang Y, Dai X, Liu Y, Li J, Liu Z, Yin P, et al. . MTUS1 silencing promotes E-selectin production through p38 MAPK-dependent CREB ubiquitination in endothelial cells. J Mol Cell Cardiol 2016;101:1–10. PubMed

Zuern C, Heimrich J, Kaufmann R, Richter K, Settmacher U, Wanner C, et al. . Down-regulation of MTUS1 in human colon tumors. Oncol Rep 2009;23:183–9. PubMed

Li X, Liu H, Yu T, Dong Z, Tang L, Sun X. Loss of MTUS1 in gastric cancer promotes tumor growth and metastasis. Neoplasma 2014;61:128–35. PubMed

Sim J, Wi YC, Park HY, Park SY, Yoon YE, Bang S, et al. . Clinicopathological significance of MTUS1 expression in patients with renal cell carcinoma. Anticancer Res 2020;40:2961–7. PubMed

Louis SN, Chow L, Rezmann L, Krezel MA, Catt KJ, Tikellis C, et al. . Expression and function of ATIP/MTUS1 in human prostate cancer cell lines. Prostate 2010;70:1563–74. PubMed PMC

Parbin S, Pradhan N, Das L, Saha P, Deb M, Sengupta D, et al. . DNA methylation regulates microtubule-associated tumor suppressor 1 in human non-small cell lung carcinoma. Exp Cell Res 2019;374:323–32. PubMed

Gu Y, Liu S, Zhang X, Chen G, Liang H, Yu M, et al. . Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer. Protein Cell 2017;8:455–66. PubMed PMC

Kara M, Kaplan M, Bozgeyik I, Ozcan O, Celik OI, Bozgeyik E, et al. . MTUS1 tumor suppressor and its miRNA regulators in fibroadenoma and breast cancer. Gene 2016;587:173–7. PubMed

Lv D-B, Zhang J-Y, Gao K, Yu Z-H, Sheng W-C, Yang G, et al. . MicroRNA-765 targets MTUS1 to promote the progression of osteosarcoma via mediating ERK/EMT pathway. Eur Rev Med Pharmacol Sci 2019;23:4618–28. PubMed

Ozcan O, Kara M, Yumrutas O, Bozgeyik E, Bozgeyik I, Celik OI. MTUS1 and its targeting miRNAs in colorectal carcinoma: significant associations. Tumor Biol 2016;37:6637–45. PubMed

Ding X, Zhang N, Cai Y, Li S, Zheng C, Jin Y, et al. . Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma. Mol Oncol 2012;6:73–80. PubMed PMC

Bellance N, Furt F, Melser S, Lalou C, Thoraval D, Maneta-Peyret L, et al. . Doxorubicin inhibits phosphatidylserine decarboxylase and modifies mitochondrial membrane composition in HeLa cells. Int J Mol Sci 2020;21:1317. PubMed PMC

Palka J, Oscilowska I, Szoka L. Collagen metabolism as a regulator of proline dehydrogenase/proline oxidase-dependent apoptosis/autophagy. Amino Acids 2021;4:1438–2199. PubMed PMC

Xu YQ, Long X, Han M, Huang MQ, Lu JF, Sun XD, et al. . Clinical benefit of COX-2 inhibitors in the adjuvant chemotherapy of advanced non-small cell lung cancer: a systematic review and meta-analysis. World J Clin Cases 2021;9:581–601. PubMed PMC

Jung YS, Park JI. Wnt signaling in cancer: therapeutic targeting of Wnt signaling beyond β-catenin and the destruction complex. Exp Mol Med 2020;52:183–91. PubMed PMC

Wheeler D, Dunn E, Harari P. Understanding resistance to EGFR inhibitors—impact on future treatment strategies. Nat Rev Clin Oncol 2010;7:493–507. PubMed PMC

Kancherla P, Daneshvar M, Sager RA, Mollapour M, Bratslavsky G. Fumarate hydratase as a therapeutic target in renal cancer. Expert Opin Ther Targets 2020;24:923–36. PubMed

Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 2006;5:493–506. PubMed

Gertz M, Nguyen GTT, Fischer F, Suenkel B, Schlicker C, Fränzel B, et al. . A molecular mechanism for direct sirtuin activation by resveratrol. PLoS One 2012;7:e49761. PubMed PMC

Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, et al. . Potential adverse effects of resveratrol: a literature review. Int J Mol Sci 2020;21:2084. PubMed PMC

Pillai VB, Samant S, Sundaresan NR, Raghuraman H, Kim G, Bonner MY, et al. . Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nat Commun 2015;6:6656. PubMed PMC

Pillai VB, Kanwal A, Fang YH, Sharp WW, Samant S, Arbiser J, et al. . Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice. Oncotarget 2017;8:34082–98. PubMed PMC

Wei L, Zhou Y, Dai Q, Qiao C, Zhao L, Hui H, et al. . Oroxylin A induces dissociation of hexokinase II from the mitochondria and inhibits glycolysis by SIRT3-mediated deacetylation of cyclophilin D in breast carcinoma. Cell Death Dis 2013;4:e601. PubMed PMC

Marsboom G, Toth PT, Ryan JJ, Hong Z, Wu X, Fang YH, et al. . Dynamin-related protein 1-mediated mitochondrial mitotic fission permits hyperproliferation of vascular smooth muscle cells and offers a novel therapeutic target in pulmonary hypertension. Circ Res 2012;110:1484–97. PubMed PMC

Lu C, Stewart DJ, Lee JJ, Ji L, Ramesh R, Jayachandran G, et al. . Phase I clinical trial of systemically administered TUSC2(FUS1)-nanoparticles mediating functional gene transfer in humans. PLoS One 2012;7:e34833. PubMed PMC

Deng WG, Wu G, Ueda K, Xu K, Roth JA, Ji L. Enhancement of antitumor activity of cisplatin in human lung cancer cells by tumor suppressor FUS1. Cancer Gene Ther 2008;15:29–39. PubMed

Xiaobo C, Majidi M, Feng M, Shao R, Wang J, Zhao Y, et al. . TUSC2(FUS1)-erlotinib induced vulnerabilities in epidermal growth factor receptor(EGFR) wildtype non-small cell lung cancer(NSCLC) targeted by the repurposed drug auranofin. Sci Rep 2016;6:35741. PubMed PMC

Khatri A, Gu JJ, McKernan CM, Xu X, Pendergast AM. ABL kinase inhibition sensitizes primary lung adenocarcinomas to chemotherapy by promoting tumor cell differentiation. Oncotarget 2019;10:1874–86. PubMed PMC

Moog S, Lussey-Lepoutre C, Favier J. Epigenetic and metabolic reprogramming of SDH-deficient paragangliomas. Endocr Relat Cancer 2020;27:R451–R63. PubMed

LACTB induces cancer cell death through the activation of the intrinsic caspase-independent pathway in breast cancer

LACTB exerts tumor suppressor properties in epithelial ovarian cancer through regulation of Slug