Gamma smooth muscle actin as a new potential marker of cancer-associated fibroblasts

. 2025 Sep 19 ; 163 (1) : 93. [epub] 20250919

Jazyk angličtina Země Německo Médium electronic

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40971055

Grantová podpora
National Institute for Cancer Research (Programme EXCELES, ID Project No. LX22NPO5102) Ministerstvo Školství, Mládeže a Tělovýchovy
COOPERATIO-Onco Univerzita Karlova v Praze
NW24-03-00459 Ministerstvo Zdravotnictví Ceské Republiky

Odkazy

PubMed 40971055
PubMed Central PMC12449396
DOI 10.1007/s00418-025-02419-9
PII: 10.1007/s00418-025-02419-9
Knihovny.cz E-zdroje

Cancer-associated fibroblasts (CAFs) represent an important component of the cancer ecosystem, influencing the broad scale of biological properties of tumour cells, including the capacity for metastasis formation. An important CAF subpopulation, known as myCAFs, typically expresses α-smooth muscle actin. Transcriptomic analysis demonstrated that activated fibroblasts isolated from various pathological tissues also express the ACTG2 gene encoding γ-smooth muscle actin. This was further validated by immunocytochemistry. Using the scratch test in vitro, it was possible to demonstrate that γ-smooth muscle actin may be associated with the epithelial-mesenchymal transition, which was also shown by transcriptomic analysis. The presence of γ-smooth muscle actin-positive fibroblasts in histopathological sections of human tumours verified the expression of this protein as a new potential marker of CAFs.

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Allison SJ (2015) Fibrosis: targeting EMT to reverse renal fibrosis. Nature Rev Nephrol 11:565. 10.1038/nrneph.2015.133 PubMed

Arnoldi R, Hiltbrunner A, Dugina V, Tille JC, Chaponnier C (2013) Smooth muscle actin isoforms: a tug of war between contraction and compliance. Eur J Cell Biol 92:187–200. 10.1016/j.ejcb.2013.06.002 PubMed

Benzoubir N, Mussini C, Lejamte C et al (2015) Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma. PLoS ONE 10:e0130559. 10.1371/journal.pone.0130559 PubMed PMC

Bond JE, Ho TQ, Selim MA, Hunter CL, Bowers EV, Levinson H (2011) Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodelling. Lab Invest 91:499–508. 10.1038/labinvest.2010.181 PubMed PMC

Boutros R, Byrne JA (2005) D53 (TPD52L1) is a cell cycle-regulated protein maximally expressed at the G2-M transition in breast cancer cells. Exp Cell Res 310:152–165. 10.1016/j.yexcr.2005.07.009 PubMed

Ceausu AR, Ciolofan A, Cimpean AM, Maghet A, Mederle O, Raica M (2018) The mesenchymal–epithelial and epithelial–mesenchymal cellular plasticity of liver metastases with digestive origin. Anticancer Res. 10.21873/anticanres.12288 PubMed

Chapman HA (2011) Epithelial-mesenchymal interactions in pulmonary fibrosis. Ann Rev Physiol 73:413–435. 10.1146/annurev-physiol-012110-142225 PubMed

Chen X, Wang J, Peng X et al (2020) Comprehensive analysis of biomarkers for prostate cancer based on weighted gene co-expression network analysis. Medicine USA 99:e19628. 10.1097/MD.0000000000019628e19628 PubMed PMC

Chen Y, Liang Z, Lai M (2024) Targeting the devil: strategies against cancer-associated fibroblasts in colorectal cancer. Transl Res 270:81–93. 10.1016/j.trsl.2024.04.003 PubMed

Cipolla MJ, Gokina NI, Osol G (2002) Pressure-induced actin polymerization in vascular smooth muscle as a mechanism underlying myogenic behavior. FASEB J 16:72–76. 10.1096/cj.01-0104hyp PubMed

Clevers H (2011) The cancer stem cell: premises, promises and challenges. Nat Med 17:313–319. 10.1038/nm.2304 PubMed

Collins RRJ, Barth B, Megison S et al (2019) ACTG2-associated visceral myopathy with chronic intestinal pseudoobstruction, intestinal malrotation, hypertrophic pyloric stenosis, choledochal cyst, and a novel missense mutation. Int J Surg Pathol 27:77–83. 10.1177/1066896918786586 PubMed PMC

Cords L, Engler S, Haberecker M et al (2024) Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer. Cancer Cell 42:396–412. 10.1016/j.ccell.2023.12.021 PubMed PMC

D’Ambrosio M, Gil J (2023) Reshaping of the tumor microenvironment by cellular senescence: An opportunity for senotherapies. Dev Cell 58:1007–1021. 10.1016/j.devcel.2023.05.010 PubMed

Duan Y, Zhang X, Ying H et al (2023) Targeting MFAP5 in cancer-associated fibroblasts sensitizes pancreatic cancer to PD-L1-based immunochemotherapy via remodeling the matrix. Oncogene 42:2061–2073. 10.1038/s41388-023-02711-9 PubMed PMC

Dvoránková B, Smetana K Jr, Chovanec M et al (2005) Transient expression of keratin 19 is induced in originally negative interfollicular epidermal cells by adhesion of suspended cells. Int J Mol Med 16(1):525–531 PubMed

Dvoránková B, Szabo P, Kodet O et al (2017) Intercellular crosstalk in human malignant melanoma. Protoplasma 254:1143–1150. 10.1007/s00709-016-1038-z PubMed

Dvořánková B, Lacina L, Smetana K Jr (2019) Isolation of normal fibroblasts and their cancer-associated counterparts (CAFs) for biomedical research. Methods Mol Biol 1879:393–406. 10.1007/7651_2018_137 PubMed

Gál P, Brábek J, Holub M et al (2022) Autoimmunity, cancer and COVID-19 abnormally activate wound healing pathways: critical role of inflammation. Histochem Cell Biol 158:415–434. 10.1007/s00418-022-02140-x PubMed PMC

Geng X, Chen H, Zhao L et al (2021) Cancer-associated fibroblast (CAF) heterogeneity and targeting therapy of CAFs in pancreatic cancer. Front Cell Dev Biol 9:655152. 10.3389/fcell.2021.655152 PubMed PMC

Gunst SJ, Zhang W (2008) Actin cytoskeletal dynamics in smooth muscle: a new paradigm for the regulation of smooth muscle contraction. Am J Physiol Cell Physiol 295:C575-587. 10.1152/ajpcell.00253.2008 PubMed PMC

Han C, Liu T, Yin R (2020) Biomarkers for cancer-associated fibroblasts. Biomark Res 8:64. 10.1186/s40364-020-00245-w PubMed PMC

Han C, Leonardo TR, Romana-Souza B et al (2023a) Microfibril-associated protein 5 and the regulation of skin scar formation. Sci Rep 13:8728. 10.1038/s41598-023-35558-x PubMed PMC

Han L, Wu Y, Fang K et al (2023b) The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis. Nat Commun 14:1. 10.1038/s41467-022-34464-6 PubMed PMC

Hashmi SK, Barka V, Yang C, Schneider S, Svitkina TM, Heuckeroth RO (2020) Pseudo-obstruction-inducing ACTG2R257C alters actin organization and function. JCI Insight 5:e140604. 10.1172/jci.insight.140604 PubMed PMC

He Y, Shi Q, Ling Y, Guo H et al (2024) ABLIM1, a novel ubiquitin E3 ligase, promotes growth and metastasis of colorectal cancer through targeting IĸBα ubiquitination and activating NF-ĸB signaling. Cell Death Differ 31:203–216. 10.1038/s41418-024-01256-y PubMed PMC

Hong Q, Li B, Cai X, Lv Z, Cai S, Zhong Y, Wen B (2021) Transcriptomic analyses of the adenoma-carcinoma sequence identify hallmarks associated with the onset of colorectal cancer. Front Oncol 11:704531. 10.3389/fonc.2021.704531 PubMed PMC

Huang XY, Fu FY, Qian K et al (2024) CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1. Mol Cell Biochem 480:203–215. 10.1007/s11010-024-04932-2 PubMed

Jin H, Liu B, Guo X et al (2023) MYLK and CALD1 as molecular targets in bladder cancer. Medicine (Baltimore) 102:e3630.2. 10.1097/MD.0000000000036302 PubMed PMC

Jung H, Kim B, Moon BI, Oh ES (2016) Cytokeratin 18 is necessary for initiation of TGF-β1-induced epithelial–mesenchymal transition in breast epithelial cells. Mol Cell Biochem 423:21–28. 10.1007/s11010-016-2818-7 PubMed

Kellermann MG, Sobral LM, da Silva SD et al (2008) Mutual paracrine effects of oral squamous cell carcinoma cells and normal oral fibroblasts: induction of fibroblast to myofibroblast transdifferentiation and modulation of tumor cell proliferation. Oral Oncol 44:509–517. 10.1016/j.oraloncology.2007.07.001 PubMed

Khan AQ, Hasan A, Mir SS, Rashid K, Uddin S, Steinhoff M (2024) Exploiting transcription factors to target EMT and cancer stem cells for tumor modulation and therapy. Semin Cancer Biol 100:1–16. 10.1016/j.semcancer.2024.03.002 PubMed

Labernadie A, Kato T, Brugués A et al (2017) A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat Cell Biol 19:224–237. 10.1038/ncb3478 PubMed PMC

Lacina L, Brábek J, Král V, Kodet O, Smetana K Jr (2019) Interleukin-6: A molecule with complex biological impact in cancer. Histol Histopathol 34:125–136. 10.14670/HH-18-033 PubMed

Lacina L, Szabo P, Klepáček I, Kolář M, Smetana K Jr (2023) Cancer-Associated Fibroblasts and Their Role in Cancer Progression. In N. Rezaei (Ed.), Cancer Research: An Interdisciplinary Approach (pp. 103–133). Springer Nature Switzerland. 10.1007/16833_2022_79

Lei Y, Jamal M, Zeng X et al (2022) Insulin receptor substrate 1(IRS1) is related with lymph node metastases and prognosis in esophageal squamous cell carcinoma. Gene 835:146651. 10.1016/j.gene.2022.146651 PubMed

Liang CC, Park AY, Guan JL (2007) In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2:329–333. 10.1038/nprot.2007.30 PubMed

Lin ZY, Chuang WL (2012) Genes responsible for the characteristics of primary cultured invasive phenotype hepatocellular carcinoma cells. Biomed Pharmacother 66:454–458. 10.1016/j.biopha.2012.04.001 PubMed

Lin Z, Li G, Jiang K, Li Z, Liu T (2024) Cancer therapy resistance mediated by cancer-associated fibroblast-derived extracellular vesicles: biological mechanisms to clinical significance and implications. Mol Cancer 23:191. 10.1186/s12943-024-02106-8 PubMed PMC

Liu H, Xiang P, Miao W, Liu H, Shen H, Xue S (2023) Analysis of the regulatory effect of ACTG2 on biological behavior of bladder cancer cells based on database screening. Cell Mol Biol 69(1):125–130. 10.14715/cmb/2022.69.1.22 PubMed

Liu Q, Yao F, Wu L et al (2024) Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies. Clin Transl Oncol 26:2395–2417. 10.1007/s12094-024-03492-7 PubMed

McHugh KM, Crawford K, Lessard JL (1991) A comprehensive analysis of the developmental and tissue-specific expression of the isoactin multigene family in the rat. Dev Biol 148:442–458. 10.1016/0012-1606(91)90263-3 PubMed

McLeish KR, Fernandes MJ (2023) Understanding inhibitory receptor function in neutrophils through the lens of CLEC12A. Immunol Rev 314:50–68. 10.1111/imr.13174 PubMed

Monteran L, Erez N (2023) MyCAFs are better than yours: targeting myofibroblasts potentiates immunotherapy. Trends Cancer 9:1–2. 10.1016/j.trecan.2022.11.001 PubMed

Morioka K, Takano-Ohmuro H (2016) Localizations of γ-actins in skin, hair, vibrissa, arrector pili muscle and other hair appendages of developing rats. Acta Histochem Cytochem 49:47–65. 10.1267/ahc.15031 PubMed PMC

Muhl L, Genové G, Leptidis S et al (2020) Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination. Nat Commun 11:4493. 10.1038/s41467-020-17740-1 PubMed PMC

Nakamura M, Tokura Y (2011) Expression of SNAI1 and TWIST1 in the eccrine glands of patients with systemic sclerosis: possible involvement of epithelial-mesenchymal transition in the pathogenesis. Br J Dermatol 164:204–205. 10.1111/j.1365-2133.2010.10021.x PubMed

Nam MW, Kim CW, Choi KC (2022) Epithelial-mesenchymal transition-inducing factors involved in the progression of lung cancers. Biomol Ther 30:213–220. 10.4062/biomolther.2021.178 PubMed PMC

Neumann K, Castiñeiras-Vilariño M, Höckendorf U et al (2014) Clec12a is an inhibitory receptor for uric acid crystals that regulates inflammation in response to cell death. Immunity 40:389–399. 10.1016/j.immuni.2013.12.015 PubMed

Novotný J, Strnadová K, Dvořánková B et al (2020) Single-cell RNA sequencing unravels heterogeneity of the stromal niche in cutaneous melanoma heterogeneous spheroids. Cancers 12:3324. 10.3390/cancers12113324 PubMed PMC

Peng Z, Ren Z, Tong Z, Zhu Y, Zhu Y, Hu K (2023) Interactions between MFAP5 + fibroblasts and tumor-infiltrating myeloid cells shape the malignant microenvironment of colorectal cancer. J Transl Med 21:405. 10.1186/s12967-023-04281-6 PubMed PMC

Plzák J, Lacina L, Chovanec M, Dvořánková B, Szabo P, Čada Z, Smetana K Jr (2010) Epithelial-stromal interaction in squamous cell epithelium-derived tumors: An important new player in the control of tumor biological properties. Anticancer Res 30:455–462 PubMed

Qin Q, Yu R, Eriksson JE, Tsai H, Zhu H (2024) Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma therapy: challenges and opportunities. Cancer Lett 591:216859 PubMed

Qiu ZK, Yang E, Yu NZ, Zhang MZ, Zhang WC, Si LB, Wang XJ (2024) The biomarkers associated with epithelial-mesenchymal transition in human keloids. Burns 50:474–487. 10.1016/j.burns.2023.09.009 PubMed

Rašková M, Lacina L, Kejík Z et al (2022) The role of IL-6 in cancer cell invasiveness and metastasis—overview and therapeutic opportunities. Cells 11:3698z. 10.3390/cells11223698 PubMed PMC

Seifi S, Shafaei S, Shafigh E, Sahabi SM, Ghasemi H (2010) Myofibroblast stromal presence and distribution in squamous epithelial carcinomas, oral dysplasia and hyperkeratosis. Asian Pac J Cancer Prev 11:359–364 PubMed

Shahid M, Kim M, Yeon A et al (2018) Quantitative proteomic analysis reveals caffeine-perturbed proteomic profiles in normal bladder epithelial cells. Proteomics. 10.1002/pmic.201800190 PubMed PMC

Shimoda Y, Ubukata Y, Handa T et al (2018) High expression of forkhead box protein C2 is associated with aggressive phenotypes and poor prognosis in clinical hepatocellular carcinoma. BMC Cancer 18:597. 10.1186/s12885-018-4503-6 PubMed PMC

Španko M, Strnadová K, Pavlíček AJ et al (2021) IL-6 in the ecosystem of head and neck cancer: possible therapeutic perspectives. Int J Mol Sci 22:11027. 10.3390/ijms222011027 PubMed PMC

Strnad H, Lacina L, Kolář M et al (2010) Head and neck squamous cancer stromal fibroblasts produce growth factors influencing phenotype of normal human keratinocytes. Histochem Cell Biol 133:201–211. 10.1007/s00418-009-0661-6 PubMed

Strnadová K, Pfeiferová L, Přikryl P et al (2022) Exosomes produced by melanoma cells significantly influence the biological properties of normal and cancer-associated fibroblasts. Histochem Cell Biol 157:153–172. 10.1007/s00418-021-02052-2 PubMed PMC

Sun Q, Taurin S, Sethakorn N et al (2009) Myocardin-dependent activation of the CArG box-rich smooth muscle γ-actin gene: preferential utilization of a single CArG element through functional association with the NKX3.1 homeodomain protein. J Biol Chem 284:32582–32590. 10.1074/jbc.M109.033910 PubMed PMC

Suresh R, Diaz RJ (2021) The remodelling of actin composition as a hallmark of cancer. Transl Oncol 14:101051. 10.1016/j.tranon.2021.101051 PubMed PMC

Swanton C, Bernard E, Abbosh C et al (2024) Embracing cancer complexity: hallmarks of systemic disease. Cell 187:1589–1616. 10.1016/j.cell.2024.02.009 PubMed PMC

Takasugi M, Yoshida Y, Ohtani N (2022) Cellular senescence and the tumour microenvironment. Mol Oncol 16:3333–3351. 10.1002/1878-0261.13268 PubMed PMC

Untergasser G, Gander R, Lilg C, Lepperdinger G, Plas E, Berger P (2005) Profiling molecular targets of TGF-β1 in prostate fibroblast-to- myofibroblast transdifferentiation. Mech Ageing Dev 126:59–69. 10.1016/j.mad.2004.09.023 PubMed

Vokurka M, Lacina L, Brábek J, Kolář M, Ng YZ, Smetana K Jr (2022) Cancer-associated fibroblasts influence the biological properties of malignant tumours via paracrine secretion and exosome production. Int J Mol Sci 23:964. 10.3390/ijms23020964 PubMed PMC

Wang Y, Wang R, Li B et al (2023) Cancer associated fibroblasts in invasive tumor front promote the metastasis of oral squamous cell carcinoma through MFAP5 upregulation. SSRN Electronic J 876(1):147504. 10.2139/ssrn.4354235 PubMed

Wolf J, Rose-John S, Garbers C (2014) Interleukin-6 and its receptors: a highly regulated and dynamic system. Cytokine 70:11–20. 10.1016/j.cyto.2014.05.024 PubMed

Wu Y, Liu ZG, Shi MQ et al (2017) Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis. Biochem Biophys Res Commun 491:537–544. 10.1016/j.bbrc.2017.04.007 PubMed

Wu S, Liu M, Zhang M et al (2024) The gene expression of CALD1, CDH2, and POSTN in fibroblast are related to idiopathic pulmonary fibrosis. Front Immunol 15:275064. 10.3389/fimmu.2024.1275064 PubMed PMC

Xiang X, Niu YR, Wang ZH, Ye LL, Peng WB, Zhou Q (2022) Cancer-associated fibroblasts: vital suppressors of the immune response in the tumor microenvironment. Cytokine Growth Factor Rev 67:35–48. 10.1016/j.cytogfr.2022.07.006 PubMed

Yang S, Dong D, Bao X, Lu R, Cheng P, Zhu S, Yang G (2024) CCL21 and CLDN11 are key driving factors of lymph node metastasis in gastric cancer. Cancer Control 31:10732748241238616. 10.1177/10732748241238616 PubMed PMC

Yoon IK, Kim HK, Kim YK et al (2004) Exploration of replicative senescence-associated genes in human dermal fibroblasts by cDNA microarray technology. Exp Gerontol 39:1369–1378. 10.1016/j.exger.2004.07.002 PubMed

Zeltz C, Alam J, Liu H et al (2019) α11β1 integrin is induced in a subset of cancer- associated fibroblasts in desmoplastic tumor stroma and mediates in vitro cell migration. Cancers (Basel) 11:765. 10.3390/cancers11060765 PubMed PMC

Zhang Y, Xu L, Chen Q et al (2022) Scorpion venom polypeptide inhibits pulmonary epithelial-mesenchymal transition in systemic sclerosis-interstitial lung disease model mice by intervening TGF- β 1/Smad signaling pathway. Evidence-Based Complementary and Alternative Medicine 2022:6557486. 10.1155/2022/6557486 PubMed PMC

Zhang Y, Lv N, Li M, Liu M, Wu C (2023) Cancer-associated fibroblasts: tumor defenders in radiation therapy. Cell Death Dis 14:541. 10.1038/s41419-023-06060-z PubMed PMC

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