• This record comes from PubMed

Role of S100 Proteins in Colorectal Carcinogenesis

. 2016 ; 2016 () : 2632703. [epub] 20160106

Status PubMed-not-MEDLINE Language English Country United States Media print-electronic

Document type Journal Article, Review

The family of S100 proteins represents 25 relatively small (9-13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κβ signaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy.

See more in PubMed

Deloulme J. C., Mbele G. O., Baudier J. S100 proteins. From purification to functions. Methods in Molecular Biology. 2002;172:185–198. PubMed

Donato R., Cannon B. R., Sorci G., et al. Functions of S100 proteins. Current Molecular Medicine. 2013;13(1):24–57. doi: 10.2174/156652413804486214. PubMed DOI PMC

Moore B. W., McGregor D. Chromatographic and electrophoretic fractionation of soluble proteins of brain and liver. The Journal of Biological Chemistry. 1965;240:1647–1653. PubMed

Rubin A. L., Stenzel K. H. In vitro synthesis of brain protein. Proceedings of the National Academy of Sciences of the United States of America. 1965;53(5):963–968. PubMed PMC

Kretsinger R. H., Nockolds C. E. Carp muscle calcium-binding protein. II. Structure determination and general description. The Journal of Biological Chemistry. 1973;248(9):3313–3326. PubMed

Suzuki F., Nakajima T., Kato K. Peripheral distribution of nervous-system specific S100 protein in rat. Journal of Biochemistry. 1982;92(3):835–838. PubMed

Kawasaki H., Nakayama S., Kretsinger R. H. Classification and evolution of EF-hand proteins. Biometals. 1998;11(4):277–295. doi: 10.1023/a:1009282307967. PubMed DOI

Weinman S. Calcium-binding proteins: an overview. Journal de Biologie Buccale. 1991;19(1):90–98. PubMed

Santamaria-Kisiel L., Rintala-Dempsey A. C., Shaw G. S. Calcium-dependent and -independent interactions of the S100 protein family. Biochemical Journal. 2006;396(2):201–214. doi: 10.1042/bj20060195. PubMed DOI PMC

Denessiouk K., Permyakov S., Denesyuk A., Permyakov E., Johnson M. S. Two structural motifs within canonical EF-hand calcium-binding domains identify five different classes of calcium buffers and sensors. PLoS ONE. 2014;9(10) doi: 10.1371/journal.pone.0109287.e109287 PubMed DOI PMC

Kraemer A. M., Saraiva L. R., Korsching S. I. Structural and functional diversification in the teleost S100 family of calcium-binding proteins. BMC Evolutionary Biology. 2008;8(1, article 48) doi: 10.1186/1471-2148-8-48. PubMed DOI PMC

Hanahan D., Weinberg R. A. The hallmarks of cancer. Cell. 2000;100(1):57–70. doi: 10.1016/s0092-8674(00)81683-9. PubMed DOI

Hanahan D., Weinberg R. A. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi: 10.1016/j.cell.2011.02.013. PubMed DOI

International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Lyon, France: IARC; 2013.

Chen H., Xu C., Jin Q., Liu Z. S100 protein family in human cancer. American Journal of Cancer Research. 2014;4(2):89–115. PubMed PMC

Ghavami S., Kerkhoff C., Chazin W. J., et al. S100A8/9 induces cell death via a novel, RAGE-independent pathway that involves selective release of Smac/DIABLO and Omi/HtrA2. Biochimica et Biophysica Acta—Molecular Cell Research. 2008;1783(2):297–311. doi: 10.1016/j.bbamcr.2007.10.015. PubMed DOI

Korndörfer I. P., Brueckner F., Skerra A. The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting α-helices can determine specific association of two EF-hand proteins. Journal of Molecular Biology. 2007;370(5):887–898. doi: 10.1016/j.jmb.2007.04.065. PubMed DOI

Kehl-Fie T. E., Chitayat S., Hood M. I., et al. Nutrient metal sequestration by calprotectin inhibits bacterial superoxide defense, enhancing neutrophil killing of Staphylococcus aureus . Cell Host and Microbe. 2011;10(2):158–164. doi: 10.1016/j.chom.2011.07.004. PubMed DOI PMC

Ryckman C., Vandal K., Rouleau P., Talbot M., Tessier P. A. Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. The Journal of Immunology. 2003;170(6):3233–3242. doi: 10.4049/jimmunol.170.6.3233. PubMed DOI

Vogl T., Tenbrock K., Ludwig S., et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nature Medicine. 2007;13(9):1042–1049. doi: 10.1038/nm1638. PubMed DOI

Sinha P., Okoro C., Foell D., Freeze H. H., Ostrand-Rosenberg S., Srikrishna G. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. The Journal of Immunology. 2008;181(7):4666–4675. doi: 10.4049/jimmunol.181.7.4666. PubMed DOI PMC

Hiratsuka S., Watanabe A., Aburatani H., Maru Y. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nature Cell Biology. 2006;8(12):1369–1375. doi: 10.1038/ncb1507. PubMed DOI

Saha A., Lee Y.-C., Zhang Z., Chandra G., Su S.-B., Mukherjee A. B. Lack of an endogenous anti-inflammatory protein in mice enhances colonization of B16F10 melanoma cells in the lungs. The Journal of Biological Chemistry. 2010;285(14):10822–10831. doi: 10.1074/jbc.m109.083550. PubMed DOI PMC

Ghavami S., Kerkhoff C., Los M., Hashemi M., Sorg C., Karami-Tehrani F. Mechanism of apoptosis induced by S100A8/A9 in colon cancer cell lines: the role of ROS and the effect of metal ions. Journal of Leukocyte Biology. 2004;76(1):169–175. doi: 10.1189/jlb.0903435. PubMed DOI

Ghavami S., Rashedi I., Dattilo B. M., et al. S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and MAP kinase-dependent pathway. Journal of Leukocyte Biology. 2008;83(6):1484–1492. doi: 10.1189/jlb.0607397. PubMed DOI PMC

Ichikawa M., Williams R., Wang L., Vogl T., Srikrishna G. S100A8/A9 activate key genes and pathways in colon tumor progression. Molecular Cancer Research. 2011;9(2):133–148. doi: 10.1158/1541-7786.MCR-10-0394. PubMed DOI PMC

Turovskaya O., Foell D., Sinha P., et al. RAGE, carboxylated glycans and S100A8/A9 play essential roles in colitis-associated carcinogenesis. Carcinogenesis. 2008;29(10):2035–2043. doi: 10.1093/carcin/bgn188. PubMed DOI PMC

Lehmann F. S., Trapani F., Fueglistaler I., et al. Clinical and histopathological correlations of fecal calprotectin release in colorectal carcinoma. World Journal of Gastroenterology. 2014;20(17):4994–4999. doi: 10.3748/wjg.v20.i17.4994. PubMed DOI PMC

Schmidt-Hansen B., Örnås D., Grigorian M., et al. Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene. 2004;23(32):5487–5495. doi: 10.1038/sj.onc.1207720. PubMed DOI

Ebralidze A., Tulchinsky E., Grigorian M., et al. Isolation and characterization of a gene specifically expressed in different metastatic cells and whose deduced gene product has a high degree of homology to a Ca2+-binding protein family. Genes & development. 1989;3(7):1086–1093. doi: 10.1101/gad.3.7.1086. PubMed DOI

Liu Y., Tang W., Wang J., et al. Clinicopathological and prognostic significance of S100A4 overexpression in colorectal cancer: a meta-analysis. Diagnostic Pathology. 2013;8, article 181 doi: 10.1186/1746-1596-8-181. PubMed DOI PMC

Boye K., Nesland J. M., Sandstad B., Mælandsmo G. M., Flatmark K. Nuclear S100A4 is a novel prognostic marker in colorectal cancer. European Journal of Cancer. 2010;46(16):2919–2925. doi: 10.1016/j.ejca.2010.07.013. PubMed DOI

Sack U., Stein U. Wnt up your mind—intervention strategies for S100A4-induced metastasis in colon cancer. General Physiology and Biophysics. 2009;28:F55–F64. PubMed

Kriajevska M., Fischer-Larsen M., Moertz E., et al. Liprin beta 1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1) The Journal of Biological Chemistry. 2002;277(7):5229–5235. doi: 10.1074/jbc.m110976200. PubMed DOI

Grigorian M., Andresen S., Tulchinsky E., et al. Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein: functional consequences of their interaction. The Journal of Biological Chemistry. 2001;276(25):22699–22708. doi: 10.1074/jbc.m010231200. PubMed DOI

Semov A., Moreno M. J., Onichtchenko A., et al. Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. The Journal of Biological Chemistry. 2005;280(21):20833–20841. doi: 10.1074/jbc.m412653200. PubMed DOI

Rubinfeld B., Albert I., Porfiri E., Fiol C., Munemitsu S., Polakis P. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996;272(5264):1023–1026. doi: 10.1126/science.272.5264.1023. PubMed DOI

Mann B., Gelos M., Siedow A., et al. Target genes of β-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(4):1603–1608. doi: 10.1073/pnas.96.4.1603. PubMed DOI PMC

Sack U., Walther W., Scudiero D., et al. S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells. Molecular Biology of the Cell. 2011;22(18):3344–3354. doi: 10.1091/mbc.e10-09-0739. PubMed DOI PMC

Stein U., Arlt F., Smith J., et al. Intervening in β-catenin signaling by sulindac inhibits S100A4-dependent colon cancer metastasis. Neoplasia. 2011;13(2):131–144. doi: 10.1593/neo.101172. PubMed DOI PMC

Komatsu K., Andoh A., Ishiguro S., et al. Increased expression of S100A6 (calcyclin), a calcium-binding protein of the S100 family, in human colorectal adenocarcinomas. Clinical Cancer Research. 2000;6(1):172–177. PubMed

Kilańczyk E., Graczyk A., Ostrowska H., Kasacka I., Leśniak W., Filipek A. S100A6 is transcriptionally regulated by β-catenin and interacts with a novel target, lamin A/C, in colorectal cancer cells. Cell Calcium. 2012;51(6):470–477. doi: 10.1016/j.ceca.2012.04.005. PubMed DOI

Melle C., Ernst G., Schimmel B., et al. Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma. International Journal of Oncology. 2006;28(1):195–200. PubMed

Huang M.-Y., Wang H.-M., Tok T.-S., et al. EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 as potential prognostic markers for postoperative Taiwanese colorectal cancer patients. DNA and Cell Biology. 2012;31(4):625–635. doi: 10.1089/dna.2011.1365. PubMed DOI

Becker T., Gerke V., Kube E., Weber K. S100P, a novel Ca2+-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties. European Journal of Biochemistry. 1992;207(2):541–547. doi: 10.1111/j.1432-1033.1992.tb17080.x. PubMed DOI

Lam F. F., Jankova L., Dent O. F., et al. Identification of distinctive protein expression patterns in colorectal adenoma. Proteomics Clinical Applications. 2010;4(1):60–70. doi: 10.1002/prca.200900084. PubMed DOI

Chandramouli A., Mercado-Pimentel M. E., Hutchinson A., et al. The induction of S100p expression by the Prostaglandin E2 (PGE2)/EP4 receptor signaling pathway in colon cancer cells. Cancer Biology & Therapy. 2014;10(10):1056–1066. doi: 10.4161/cbt.10.10.13373. PubMed DOI PMC

Cao L. Y., Yin Y., Li H., Jiang Y., Zhang H. F. Expression and clinical significance of S100A2 and p63 in esophageal carcinoma. World Journal of Gastroenterology. 2009;15(33):4183–4188. PubMed PMC

Lee O.-J., Hong S.-M., Razvi M. H., et al. Expression of calcium-binding proteins S100A2 and S100A4 in Barrett's adenocarcinomas. Neoplasia. 2006;8(10):843–850. doi: 10.1593/neo.06481. PubMed DOI PMC

Zaidi A. H., Gopalakrishnan V., Kasi P. M., et al. Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma. Cancer. 2014;120(24):3902–3913. doi: 10.1002/cncr.28963. PubMed DOI PMC

Liu Y.-F., Liu Q.-Q., Wang X., Luo C.-H. Clinical significance of S100A2 expression in gastric cancer. Tumor Biology. 2014;35(4):3731–3741. doi: 10.1007/s13277-013-1495-3. PubMed DOI

Zhang Q., Zhu M., Cheng W., et al. Downregulation of 425G>A variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer. Journal of Cancer Research and Clinical Oncology. 2015;141(4):691–703. doi: 10.1007/s00432-014-1830-0. PubMed DOI PMC

Ling Z., Li R. Clinicopathological and prognostic value of S100A4 expression in gastric cancer: a meta-analysis. International Journal of Biological Markers. 2014;29(2):e99–e111. doi: 10.5301/jbm.5000054. PubMed DOI

Wang Y., Zhou L.-B., Li X.-H. S100A4 expression and prognosis of gastric cancer: a meta-analysis. Genetics and Molecular Research. 2014;13(4):10398–10403. doi: 10.4238/2014.december.12.1. PubMed DOI

Zhang J., Zhang K., Jiang X., Zhang J. S100A6 as a potential serum prognostic biomarker and therapeutic target in gastric cancer. Digestive Diseases and Sciences. 2014;59(9):2136–2144. doi: 10.1007/s10620-014-3137-z. PubMed DOI

Liu J., Li X., Dong G. L., et al. In silico analysis and verification of S100 gene expression in gastric cancer. BMC Cancer. 2008;8(1, article 261) doi: 10.1186/1471-2407-8-261. PubMed DOI PMC

Wang L., Chang E. W. Y., Wong S., Ong S.-M., Chong D. Q. Y., Ling K. L. Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. Journal of Immunology. 2013;190(2):794–804. doi: 10.4049/jimmunol.1202088. PubMed DOI

Bachet J.-B., Maréchal R., Demetter P., et al. S100A2 is a predictive biomarker of adjuvant therapy benefit in pancreatic adenocarcinoma. European Journal of Cancer. 2013;49(12):2643–2653. doi: 10.1016/j.ejca.2013.04.017. PubMed DOI

Ji Y.-F., Huang H., Jiang F., Ni R.-Z., Xiao M.-B. S100 family signaling network and related proteins in pancreatic cancer (review) International Journal of Molecular Medicine. 2014;33(4):769–776. doi: 10.3892/ijmm.2014.1633. PubMed DOI

Ohuchida K., Mizumoto K., Ohhashi S., et al. S100A11, a putative tumor suppressor gene, is overexpressed in pancreatic carcinogenesis. Clinical Cancer Research. 2006;12(18):5417–5422. doi: 10.1158/1078-0432.CCR-06-0222. PubMed DOI

Kuźnicki J., Filipek A. Purification and properties of a novel Ca2+-binding protein (10.5 kDa) from Ehrlich-ascites-tumour cells. Biochemical Journal. 1987;247(3):663–667. doi: 10.1042/bj2470663. PubMed DOI PMC

Stulík J., Österreicher J., Koupilová K., et al. Differential expression of the Ca2+ binding S100A6 protein in normal, preneoplastic and neoplastic colon mucosa. European Journal of Cancer. 2000;36(8):1050–1059. doi: 10.1016/s0959-8049(00)00043-5. PubMed DOI

Leclerc E., Fritz G., Weibel M., Heizmann C. W., Galichet A. S100B and S100A6 differentially modulate cell survival by interacting with distinct RAGE (receptor for advanced glycation end products) immunoglobulin domains. The Journal of Biological Chemistry. 2007;282(43):31317–31331. doi: 10.1074/jbc.m703951200. PubMed DOI

Duan L., Wu R., Zou Z., et al. S100A6 stimulates proliferation and migration of colorectal carcinoma cells through activation of the MAPK pathways. International Journal of Oncology. 2014;44(3):781–790. doi: 10.3892/ijo.2013.2231. PubMed DOI

Melle C., Ernst G., Schimmel B., Bleul A., von Eggeling F. Colon-derived liver metastasis, colorectal carcinoma, and hepatocellular carcinoma can be discriminated by the Ca2+-binding proteins S100A6 and S100A11. PLoS ONE. 2008;3(12) doi: 10.1371/journal.pone.0003767.e3767 PubMed DOI PMC

He H., Li J., Weng S., Li M., Yu Y. S100A11: diverse function and pathology corresponding to different target proteins. Cell Biochemistry and Biophysics. 2009;55(3):117–126. doi: 10.1007/s12013-009-9061-8. PubMed DOI

Sakaguchi M., Miyazaki M., Inoue Y., et al. Relationship between contact inhibition and intranuclear S100C of normal human fibroblasts. Journal of Cell Biology. 2000;149(6):1193–1206. doi: 10.1083/jcb.149.6.1193. PubMed DOI PMC

Cecil D. L., Johnson K., Rediske J., Lotz M., Schmidt A. M., Terkeltaub R. Inflammation-induced chondrocyte hypertrophy is driven by receptor for advanced glycation end products. Journal of Immunology. 2005;175(12):8296–8302. doi: 10.4049/jimmunol.175.12.8296. PubMed DOI

Stulík J., Koupilová K., Österreicher J., et al. Protein abundance alterations in matched sets of macroscopically normal colon mucosa and colorectal carcinoma. Electrophoresis. 1999;20(18):3638–3646. doi: 10.1002/(SICI)1522-2683(19991201)20:18<3638::AID-ELPS3638>3.0.CO;2-W. PubMed DOI

Huang M.-Y., Wang H.-M., Chang H.-J., Hsiao C.-P., Wang J.-Y., Lin S.-R. Overexpression of s100b, tm4sf4, and olfm4 genes is correlated with liver metastasis in taiwanese colorectal cancer patients. DNA and Cell Biology. 2012;31(1):43–49. doi: 10.1089/dna.2011.1264. PubMed DOI PMC

Emoto Y., Kobayashi R., Akatsuka H., Hidaka H. Purification and characterization of a new member of the S-100 protein family from human placenta. Biochemical and Biophysical Research Communications. 1992;182(3):1246–1253. doi: 10.1016/0006-291x(92)91865-n. PubMed DOI

Dowen S. E., Crnogorac-Jurcevic T., Gangeswaran R., et al. Expression of S100P and its novel binding partner S100PBPR in early pancreatic cancer. The American Journal of Pathology. 2005;166(1):81–92. doi: 10.1016/s0002-9440(10)62234-1. PubMed DOI PMC

Dong L., Wang F., Yin X., et al. Overexpression of S100P promotes colorectal cancer metastasis and decreases chemosensitivity to 5-FU in vitro. Molecular and Cellular Biochemistry. 2014;389(1-2):257–264. doi: 10.1007/s11010-013-1947-5. PubMed DOI

Wang Q., Zhang Y.-N., Lin G.-L., et al. S100P, a potential novel prognostic marker in colorectal cancer. Oncology Reports. 2012;28(1):303–310. doi: 10.3892/or.2012.1794. PubMed DOI

Shen L., Sundstedt A., Ciesielski M., et al. Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models. Cancer Immunology Research. 2015;3(2):136–148. doi: 10.1158/2326-6066.cir-14-0036. PubMed DOI PMC

Raymond E., Dalgleish A., Damber J.-E., Smith M., Pili R. Mechanisms of action of tasquinimod on the tumour microenvironment. Cancer Chemotherapy and Pharmacology. 2014;73(1):1–8. doi: 10.1007/s00280-013-2321-8. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...