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Gene Review

ST14  -  suppression of tumorigenicity 14 (colon...

Homo sapiens

Synonyms: ARCI11, HAI, MT-SP1, MTSP1, Matriptase, ...
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Disease relevance of ST14


High impact information on ST14

  • Overexpression of the type II transmembrane serine protease matriptase is a highly consistent feature of human epithelial tumors [7].
  • Modest orthotopic overexpression of matriptase in the skin of transgenic mice caused spontaneous squamous cell carcinoma and dramatically potentiated carcinogen-induced tumor formation [7].
  • Matriptase-induced malignant conversion was preceded by progressive interfollicular hyperplasia, dysplasia, follicular transdifferentiation, fibrosis, and dermal inflammation [7].
  • Recombination within DXS52 (ST14) locus in family with haemophilia A [8].
  • The adaptability of the scaffold was demonstrated by the isolation of inhibitors to two additional serine proteases, MT-SP1/matriptase and Factor XIIa [9].

Chemical compound and disease context of ST14


Biological context of ST14

  • Quantitative real time PCR revealed that the expression of the TMEFF1 gene was dependent on the transfection of the ST14 gene in the RKO cell line [1].
  • In addition, the expression levels of SPINT1, ST14, HGF, and MET mRNAs in the villous tree increased over the course of gestation [13].
  • RESULTS: SNC19/ST14 gene overexpression could enhance invasion of colorectal cancer cells in vitro significantly and influence early cell adherence to ECM, but could not change cell movement significantly [2].
  • Recombination between the four loci 52A, F9, fragile X, and ST14 is significantly decreased in meioses giving rise to the affected grandsons of normal transmitting males, when compared to families where there are no apparent normal transmitting males [14].
  • In 54 informative meioses, three recombinations between the factor VIII locus and the DX13 and/or ST14 loci were observed, giving a recombination rate of 5.5% [15].

Anatomical context of ST14


Associations of ST14 with chemical compounds

  • ST14 (suppression of tumorigenicity 14) is a transmembrane serine protease that contains a serine protease catalytic (SP) domain, an SEA domain, two complement subcomponent C1r/s (CUB) domains, and four low density lipoprotein receptor class A domains [1].
  • However, up to five-fold higher levels of activated matriptase were detected in the conditioned media from the cancer cells grown in the absence of serum and S1P, when compared to non-transformed mammary epithelial cells [10].
  • Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching [17].
  • Sphingosine 1-phosphate, present in serum-derived lipoproteins, activates matriptase [18].
  • We further demonstrated that matriptase can convert hepatocyte growth factor/scattering factor to its active form, which can induce scatter of Madin-Darby canine kidney epithelial cells and can activate c-Met tyrosine phosphorylation in A549 human lung carcinoma cells [19].

Physical interactions of ST14

  • Finally, homology modeling studies suggested that TMEFF1 might form a complex with ST14 by an interaction between epidermal growth factor and CUB domains [1].
  • Indeed, all activated matriptase was detected in complexes with HAI-1 only 5 min after suramin stimulation [20].

Enzymatic interactions of ST14

  • When the membrane fraction was separated by SDS/PAGE, the IGFBP-rP1-cleaving activity comigrated with matriptase [21].

Regulatory relationships of ST14


Other interactions of ST14

  • Both are Kunitz-type serine proteinase inhibitors and inhibit not only HGFA but also other serine proteinases, such as membrane-type serine protease 1 (matriptase), plasmin, trypsin and kallikreins [26].
  • CONCLUSION: MT-SP1/matriptase induces release of proinflammatory cytokines in endothelial cells through activation of PAR-2 [22].
  • Protease-activated receptor 2 (PAR2) and single-chain urokinase-type plasminogen activator are proteins that are localized to the extracellular surface and contain the preferred MT-SP1 cleavage sequence [3].
  • Interestingly, these two genes were co-up-regulated in kidney tumors versus normal tissues, consistent with our results that showed the dependence of TMEFF1 expression on ST14 in RKO cells [1].
  • Previous studies have shown linkage between the X linked form of the disease and the Xq28 probes ST14, DX13, and F8C [27].

Analytical, diagnostic and therapeutic context of ST14


  1. Protein interaction analysis of ST14 domains and their point and deletion mutants. Ge, W., Hu, H., Ding, K., Sun, L., Zheng, S. J. Biol. Chem. (2006) [Pubmed]
  2. Effect of SNC19/ST14 gene overexpression on invasion of colorectal cancer cells. Ding, K.F., Sun, L.F., Ge, W.T., Hu, H.G., Zhang, S.Z., Zheng, S. World J. Gastroenterol. (2005) [Pubmed]
  3. Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. Takeuchi, T., Harris, J.L., Huang, W., Yan, K.W., Coughlin, S.R., Craik, C.S. J. Biol. Chem. (2000) [Pubmed]
  4. In vitro inhibition of matriptase prevents invasive growth of cell lines of prostate and colon carcinoma. Förbs, D., Thiel, S., Stella, M.C., Stürzebecher, A., Schweinitz, A., Steinmetzer, T., Stürzebecher, J., Uhland, K. Int. J. Oncol. (2005) [Pubmed]
  5. Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract. Zeng, L., Cao, J., Zhang, X. World J. Gastroenterol. (2005) [Pubmed]
  6. Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice. List, K., Currie, B., Scharschmidt, T.C., Szabo, R., Shireman, J., Molinolo, A., Cravatt, B.F., Segre, J., Bugge, T.H. J. Biol. Chem. (2007) [Pubmed]
  7. Deregulated matriptase causes ras-independent multistage carcinogenesis and promotes ras-mediated malignant transformation. List, K., Szabo, R., Molinolo, A., Sriuranpong, V., Redeye, V., Murdock, T., Burke, B., Nielsen, B.S., Gutkind, J.S., Bugge, T.H. Genes Dev. (2005) [Pubmed]
  8. Recombination within DXS52 (ST14) locus in family with haemophilia A. Kirk, H.E., Robertson, K.A., Hay, C.W., Yong, S.L., McGillivray, B.C., Growe, G.H., MacGillivray, R.T. Lancet (1987) [Pubmed]
  9. Engineering of a macromolecular scaffold to develop specific protease inhibitors. Stoop, A.A., Craik, C.S. Nat. Biotechnol. (2003) [Pubmed]
  10. Deregulated activation of matriptase in breast cancer cells. Benaud, C.M., Oberst, M., Dickson, R.B., Lin, C.Y. Clin. Exp. Metastasis (2002) [Pubmed]
  11. Purification and characterization of a complex containing matriptase and a Kunitz-type serine protease inhibitor from human milk. Lin, C.Y., Anders, J., Johnson, M., Dickson, R.B. J. Biol. Chem. (1999) [Pubmed]
  12. Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells. Kiyomiya, K., Lee, M.S., Tseng, I.C., Zuo, H., Barndt, R.J., Johnson, M.D., Dickson, R.B., Lin, C.Y. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
  13. The cytotrophoblast layer of human chorionic villi becomes thinner but maintains its structural integrity during gestation. Mori, M., Ishikawa, G., Luo, S.S., Mishima, T., Goto, T., Robinson, J.M., Matsubara, S., Takeshita, T., Kataoka, H., Takizawa, T. Biol. Reprod. (2007) [Pubmed]
  14. Analysis of linkage relationships between genetic markers around the fragile X locus with special reference to the daughters of normal transmitting males. Winter, R.M., Pembrey, M.E. Hum. Genet. (1986) [Pubmed]
  15. Carrier detection in 50 haemophilia A kindred by means of three intragenic and two extragenic restriction fragment length polymorphisms. Moodie, P., Liddell, M.B., Peake, I.R., Bloom, A.L. Br. J. Haematol. (1988) [Pubmed]
  16. Matriptase: potent proteolysis on the cell surface. List, K., Bugge, T.H., Szabo, R. Mol. Med. (2006) [Pubmed]
  17. Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1-6 GlcNAc branching. Ihara, S., Miyoshi, E., Ko, J.H., Murata, K., Nakahara, S., Honke, K., Dickson, R.B., Lin, C.Y., Taniguchi, N. J. Biol. Chem. (2002) [Pubmed]
  18. Sphingosine 1-phosphate, present in serum-derived lipoproteins, activates matriptase. Benaud, C., Oberst, M., Hobson, J.P., Spiegel, S., Dickson, R.B., Lin, C.Y. J. Biol. Chem. (2002) [Pubmed]
  19. Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. Lee, S.L., Dickson, R.B., Lin, C.Y. J. Biol. Chem. (2000) [Pubmed]
  20. Simultaneous activation and hepatocyte growth factor activator inhibitor 1-mediated inhibition of matriptase induced at activation foci in human mammary epithelial cells. Lee, M.S., Kiyomiya, K., Benaud, C., Dickson, R.B., Lin, C.Y. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  21. Identification of membrane-bound serine proteinase matriptase as processing enzyme of insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1/angiomodulin/mac25). Ahmed, S., Jin, X., Yagi, M., Yasuda, C., Sato, Y., Higashi, S., Lin, C.Y., Dickson, R.B., Miyazaki, K. FEBS J. (2006) [Pubmed]
  22. Membrane-type serine protease-1/matriptase induces interleukin-6 and -8 in endothelial cells by activation of protease-activated receptor-2: potential implications in atherosclerosis. Seitz, I., Hess, S., Schulz, H., Eckl, R., Busch, G., Montens, H.P., Brandl, R., Seidl, S., Schömig, A., Ott, I. Arterioscler. Thromb. Vasc. Biol. (2007) [Pubmed]
  23. Matriptase and HAI-1 are expressed by normal and malignant epithelial cells in vitro and in vivo. Oberst, M., Anders, J., Xie, B., Singh, B., Ossandon, M., Johnson, M., Dickson, R.B., Lin, C.Y. Am. J. Pathol. (2001) [Pubmed]
  24. HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease. Oberst, M.D., Chen, L.Y., Kiyomiya, K., Williams, C.A., Lee, M.S., Johnson, M.D., Dickson, R.B., Lin, C.Y. Am. J. Physiol., Cell Physiol. (2005) [Pubmed]
  25. Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase. Friedrich, R., Fuentes-Prior, P., Ong, E., Coombs, G., Hunter, M., Oehler, R., Pierson, D., Gonzalez, R., Huber, R., Bode, W., Madison, E.L. J. Biol. Chem. (2002) [Pubmed]
  26. Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. Kataoka, H., Miyata, S., Uchinokura, S., Itoh, H. Cancer Metastasis Rev. (2003) [Pubmed]
  27. A linkage study of a large pedigree with X linked centronuclear myopathy. Starr, J., Lamont, M., Iselius, L., Harvey, J., Heckmatt, J. J. Med. Genet. (1990) [Pubmed]
  28. Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Takeuchi, T., Shuman, M.A., Craik, C.S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
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