“S100A4”的意思、由来-开放百科全书

Function

The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein may function in motility, invasion, and tubulin polymerization. Chromosomal rearrangements and altered expression of this gene have been implicated in tumor metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified.^[2]

Interactions

Therapeutic targeting for cancer

S100A4, a member of the S100 calcium-binding protein family secreted by tumor and stromal cells, supports tumorigenesis by stimulating angiogenesis. Research demonstrated that S100A4 synergizes with vascular endothelial growth factor (VEGF), via the RAGE receptor, in promoting endothelial cell migration by increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4 led to a significant increase in tumor growth and vascularization in a human melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA technology, a dramatic decrease in tumor development of the pancreatic MIA PaCa-2 cell line was observed. Based on these results 5C3 was developed, a neutralizing monoclonal antibody against S100A4. This antibody abolished endothelial cell migration, tumor growth and angiogenesis in immunodeficient mouse xenograft models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular S100A4 inhibition is an attractive approach for the treatment of human cancer.^[5]

References

1. ^{{cite journal | vauthors = Stoler A, Bouck N | title = Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 82 | issue = 2 | pages = 570–4 | date = March 1985 | pmid = 3155863 | pmc = 397082 | doi = 10.1073/pnas.82.2.570 }}
2. ^{{cite web | title = Entrez Gene: S100A4 S100 calcium binding protein A4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6275| accessdate = }}
3. ^{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
4. ^{{cite journal | vauthors = Wang G, Rudland PS, White MR, Barraclough R | title = Interaction in vivo and in vitro of the metastasis-inducing S100 protein, S100A4 (p9Ka) with S100A1 | journal = J. Biol. Chem. | volume = 275 | issue = 15 | pages = 11141–6 | date = April 2000 | pmid = 10753920 | doi = 10.1074/jbc.275.15.11141 }}
5. ^{{cite journal | vauthors = Hernández JL, Padilla L, Dakhel S, Coll T, Hervas R, Adan J, Masa M, Mitjans F, Martinez JM, Coma S, Rodríguez L, Noé V, Ciudad CJ, Blasco F, Messeguer R | title = Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4 monoclonal antibody. | journal = PLOS ONE | volume = 8| issue = | pages = e72480| date = September 2013 | pmid = 24023743| doi = 10.1371/journal.pone.0072480 | pmc=3762817}}

Function

Interactions

Therapeutic targeting for cancer

References

Further reading