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Gene Review

S100A4  -  S100 calcium binding protein A4

Homo sapiens

Synonyms: 18A2, 42A, CAPL, Calvasculin, FSP1, ...
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Disease relevance of S100A4

  • S100A4 is correlated with the development of metastasis [1].
  • S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9 [2].
  • ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma [3].
  • Increased levels of the homodimeric calcium-binding protein, S100A4, have been shown to cause a metastatic phenotype in at least three independent model systems of breast cancer and its presence in carcinoma cells has been shown to be associated with a reduction in the survival of patients suffering from a range of different cancers [4].
  • Using surgically resected specimens, it seemed that the amount of S100A4 mRNA in adenomas was nearly equal to that in normal colonic mucosa, whereas adenocarcinomas expressed a significantly higher amount of the RNA than did the adjacent normal colonic mucosa [5].

High impact information on S100A4


Chemical compound and disease context of S100A4


Biological context of S100A4


Anatomical context of S100A4


Associations of S100A4 with chemical compounds


Physical interactions of S100A4


Regulatory relationships of S100A4


Other interactions of S100A4

  • Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy [28].
  • The interaction between S100A4 and S100A1 was also observed in vitro using affinity column chromatography and gel overlay techniques [29].
  • RESULTS: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N [30].
  • The present work demonstrates a distinct intracellular localization of S100A6, S100A4, and S100A2 in two tumor cell lines derived from metastatic epithelial breast adenocarcinoma (MDA-MB231) and cervical carcinoma (HeLa) [17].
  • It is shown that the cell lines with a low S100A4 level produced a reduced amount of immunoreactive MMP-2 at cellular subconfluence, while at confluence there was no difference compared to the control cells [24].
  • Pretreatment of chondrocytes with a JAK-3 inhibitor or with cycloheximide blocked the IL-7-mediated secretion of S100A4, but pretreatment with brefeldin A did not [31].

Analytical, diagnostic and therapeutic context of S100A4


  1. Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor. Fernandez-Fernandez, M.R., Veprintsev, D.B., Fersht, A.R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  2. S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Saleem, M., Kweon, M.H., Johnson, J.J., Adhami, V.M., Elcheva, I., Khan, N., Bin Hafeez, B., Bhat, K.M., Sarfaraz, S., Reagan-Shaw, S., Spiegelman, V.S., Setaluri, V., Mukhtar, H. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. ERBB2 up-regulates S100A4 and several other prometastatic genes in medulloblastoma. Hernan, R., Fasheh, R., Calabrese, C., Frank, A.J., Maclean, K.H., Allard, D., Barraclough, R., Gilbertson, R.J. Cancer Res. (2003) [Pubmed]
  4. Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes. Wang, G., Zhang, S., Fernig, D.G., Martin-Fernandez, M., Rudland, P.S., Barraclough, R. Oncogene (2005) [Pubmed]
  5. Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas. Takenaga, K., Nakanishi, H., Wada, K., Suzuki, M., Matsuzaki, O., Matsuura, A., Endo, H. Clin. Cancer Res. (1997) [Pubmed]
  6. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Caldas, C., Hahn, S.A., da Costa, L.T., Redston, M.S., Schutte, M., Seymour, A.B., Weinstein, C.L., Hruban, R.H., Yeo, C.J., Kern, S.E. Nat. Genet. (1994) [Pubmed]
  7. The Metastasis-Associated Gene S100A4 Is a Novel Target of beta-catenin/T-cell Factor Signaling in Colon Cancer. Stein, U., Arlt, F., Walther, W., Smith, J., Waldman, T., Harris, E.D., Mertins, S.D., Heizmann, C.W., Allard, D., Birchmeier, W., Schlag, P.M., Shoemaker, R.H. Gastroenterology (2006) [Pubmed]
  8. Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease. Lawrie, A., Spiekerkoetter, E., Martinez, E.C., Ambartsumian, N., Sheward, W.J., MacLean, M.R., Harmar, A.J., Schmidt, A.M., Lukanidin, E., Rabinovitch, M. Circ. Res. (2005) [Pubmed]
  9. Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Rosty, C., Ueki, T., Argani, P., Jansen, M., Yeo, C.J., Cameron, J.L., Hruban, R.H., Goggins, M. Am. J. Pathol. (2002) [Pubmed]
  10. Intracellular calcium-binding protein S100A4 influences injury-induced migration of white matter astrocytes. Fang, Z., Duthoit, N., Wicher, G., Källskog, O., Ambartsumian, N., Lukanidin, E., Takenaga, K., Kozlova, E.N. Acta Neuropathol. (2006) [Pubmed]
  11. Prediction of nodal spread of breast cancer by using artificial neural network-based analyses of S100A4, nm23 and steroid receptor expression. Grey, S.R., Dlay, S.S., Leone, B.E., Cajone, F., Sherbet, G.V. Clin. Exp. Metastasis (2003) [Pubmed]
  12. 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). Kriajevska, M., Fischer-Larsen, M., Moertz, E., Vorm, O., Tulchinsky, E., Grigorian, M., Ambartsumian, N., Lukanidin, E. J. Biol. Chem. (2002) [Pubmed]
  13. Up-regulation of metastasis-promoting S100A4 (Mts-1) in rheumatoid arthritis: putative involvement in the pathogenesis of rheumatoid arthritis. Klingelhöfer, J., Senolt, L., Baslund, B., Nielsen, G.H., Skibshøj, I., Pavelka, K., Neidhart, M., Gay, S., Ambartsumian, N., Hansen, B.S., Petersen, J., Lukanidin, E., Grigorian, M. Arthritis Rheum. (2007) [Pubmed]
  14. Microarray analysis of metastasis-associated gene expression profiling in a murine model of thyroid carcinoma pulmonary metastasis: identification of S100A4 (Mts1) gene overexpression as a poor prognostic marker for thyroid carcinoma. Zou, M., Famulski, K.S., Parhar, R.S., Baitei, E., Al-Mohanna, F.A., Farid, N.R., Shi, Y. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  15. Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. Maelandsmo, G.M., Flørenes, V.A., Mellingsaeter, T., Hovig, E., Kerbel, R.S., Fodstad, O. Int. J. Cancer (1997) [Pubmed]
  16. Distinct subcellular localization of calcium binding S100 proteins in human smooth muscle cells and their relocation in response to rises in intracellular calcium. Mandinova, A., Atar, D., Schäfer, B.W., Spiess, M., Aebi, U., Heizmann, C.W. J. Cell. Sci. (1998) [Pubmed]
  17. Subcellular distribution of S100 proteins in tumor cells and their relocation in response to calcium activation. Mueller, A., Bächi, T., Höchli, M., Schäfer, B.W., Heizmann, C.W. Histochem. Cell Biol. (1999) [Pubmed]
  18. Isoproterenol-induced myocardial injury resulting in altered S100A4 and S100A11 protein expression in the rat. Inamoto, S., Murao, S., Yokoyama, M., Kitazawa, S., Maeda, S. Pathol. Int. (2000) [Pubmed]
  19. Increase in production of matrix metalloproteinase 13 by human articular chondrocytes due to stimulation with S100A4: Role of the receptor for advanced glycation end products. Yammani, R.R., Carlson, C.S., Bresnick, A.R., Loeser, R.F. Arthritis Rheum. (2006) [Pubmed]
  20. Methionine aminopeptidase 2 is a new target for the metastasis-associated protein, S100A4. Endo, H., Takenaga, K., Kanno, T., Satoh, H., Mori, S. J. Biol. Chem. (2002) [Pubmed]
  21. Heterocomplex formation between metastasis-related protein S100A4 (Mts1) and S100A1 as revealed by the yeast two-hybrid system. Tarabykina, S., Kriajevska, M., Scott, D.J., Hill, T.J., Lafitte, D., Derrick, P.J., Dodson, G.G., Lukanidin, E., Bronstein, I. FEBS Lett. (2000) [Pubmed]
  22. Metastasis-associated protein S100A4 induces angiogenesis through interaction with Annexin II and accelerated plasmin formation. Semov, A., Moreno, M.J., Onichtchenko, A., Abulrob, A., Ball, M., Ekiel, I., Pietrzynski, G., Stanimirovic, D., Alakhov, V. J. Biol. Chem. (2005) [Pubmed]
  23. Characterization of the metastasis-associated protein, S100A4. Roles of calcium binding and dimerization in cellular localization and interaction with myosin. Kim, E.J., Helfman, D.M. J. Biol. Chem. (2003) [Pubmed]
  24. S100A4 regulates membrane induced activation of matrix metalloproteinase-2 in osteosarcoma cells. Mathisen, B., Lindstad, R.I., Hansen, J., El-Gewely, S.A., Maelandsmo, G.M., Hovig, E., Fodstad, O., Loennechen, T., Winberg, J.O. Clin. Exp. Metastasis (2003) [Pubmed]
  25. Suppression of metastasis-associated S100A4 gene expression by gamma-interferon in human colon adenocarcinoma cells. Takenaga, K. Br. J. Cancer (1999) [Pubmed]
  26. S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Bjørnland, K., Winberg, J.O., Odegaard, O.T., Hovig, E., Loennechen, T., Aasen, A.O., Fodstad, O., Maelandsmo, G.M. Cancer Res. (1999) [Pubmed]
  27. CCNs, fibulin-1C and S100A4 expression in leiomyoma and myometrium: inverse association with TGF-beta and regulation by TGF-beta in leiomyoma and myometrial smooth muscle cells. Luo, X., Ding, L., Chegini, N. Mol. Hum. Reprod. (2006) [Pubmed]
  28. Supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas are characterized by a differential expression of S100 proteins. Camby, I., Nagy, N., Lopes, M.B., Schäfer, B.W., Maurage, C.A., Ruchoux, M.M., Murmann, P., Pochet, R., Heizmann, C.W., Brotchi, J., Salmon, I., Kiss, R., Decaestecker, C. Brain Pathol. (1999) [Pubmed]
  29. Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1. Wang, G., Rudland, P.S., White, M.R., Barraclough, R. J. Biol. Chem. (2000) [Pubmed]
  30. Expression of S100A6 and S100A4 in matched samples of human colorectal mucosa, primary colorectal adenocarcinomas and liver metastases. Komatsu, K., Murata, K., Kameyama, M., Ayaki, M., Mukai, M., Ishiguro, S., Miyoshi, J., Tatsuta, M., Inoue, M., Nakamura, H. Oncology (2002) [Pubmed]
  31. Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes. Yammani, R.R., Long, D., Loeser, R.F. Arthritis Rheum. (2009) [Pubmed]
  32. Differential expression of S100A2 and S100A4 in lung adenocarcinomas: clinicopathological significance, relationship to p53 and identification of their target genes. Matsubara, D., Niki, T., Ishikawa, S., Goto, A., Ohara, E., Yokomizo, T., Heizmann, C.W., Aburatani, H., Moriyama, S., Moriyama, H., Nishimura, Y., Funata, N., Fukayama, M. Cancer Sci. (2005) [Pubmed]
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