Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases

Sfaxi F, Scamuffa N, Lalou C, Ma J, Metrakos P, Siegfried G, Ragg H, Bikfalvi A, Calvo F, Khatib A-M (2014)
Oncotarget 5(12): 4195-4210.

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Abstract
Liver is the most common site of metastasis from colorectal cancers, and liver of patients with liver colorectal metastasis have abnormal levels of the proprotein convertases (PCs). These proteases are involved in the activation and/or expression of various colon cancer-related mediators, making them promising targets in colorectal liver metastasis therapy. Here, we revealed that the serpin Spn4 from Drosophila melanogaster inhibits the activity of all the PCs found in the constitutive secretory pathway and represses the metastatic potential of the colon cancer cells HT-29 and CT-26. In these cells, Spn4A inhibited the processing of the PCs substrates IGF-1R and PDGF-A that associated their reduced anchorage-independent growth, invasiveness and survival in response to apoptotic agents. In vivo, Spn4A-expressing tumor cells showed repressed subcutaneous tumor development and liver metastases formation in response to their intrasplenic inoculation. In these cells Spn4A induced the expression of molecules with anti-metastatic functions and inhibited expression of pro-tumorigenic molecules. Taken together, our findings identify Spn4A as the only endogenous inhibitor of all the constitutive secretory pathway PCs, which is able to repress the metastatic potential of colon cancer cells. These results suggest the potential use of Spn4A and/or derivates as a useful adduct colorectal liver metastasis prevention.
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Sfaxi F, Scamuffa N, Lalou C, et al. Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget. 2014;5(12):4195-4210.
Sfaxi, F., Scamuffa, N., Lalou, C., Ma, J., Metrakos, P., Siegfried, G., Ragg, H., et al. (2014). Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget, 5(12), 4195-4210.
Sfaxi, F., Scamuffa, N., Lalou, C., Ma, J., Metrakos, P., Siegfried, G., Ragg, H., Bikfalvi, A., Calvo, F., and Khatib, A. - M. (2014). Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget 5, 4195-4210.
Sfaxi, F., et al., 2014. Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget, 5(12), p 4195-4210.
F. Sfaxi, et al., “Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases”, Oncotarget, vol. 5, 2014, pp. 4195-4210.
Sfaxi, F., Scamuffa, N., Lalou, C., Ma, J., Metrakos, P., Siegfried, G., Ragg, H., Bikfalvi, A., Calvo, F., Khatib, A.-M.: Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget. 5, 4195-4210 (2014).
Sfaxi, Fatma, Scamuffa, Nathalie, Lalou, Claude, Ma, Jia, Metrakos, Peter, Siegfried, Geraldine, Ragg, Hermann, Bikfalvi, Andreas, Calvo, Fabien, and Khatib, Abdel-Majid. “Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases”. Oncotarget 5.12 (2014): 4195-4210.
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37 References

Data provided by Europe PubMed Central.

Structure of a serpin-protease complex shows inhibition by deformation.
Huntington JA, Read RJ, Carrell RW., Nature 407(6806), 2000
PMID: 11057674
Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer.
Page RE, Klein-Szanto AJ, Litwin S, Nicolas E, Al-Jumaily R, Alexander P, Godwin AK, Ross EA, Schilder RJ, Bassi DE., Cell. Oncol. 29(4), 2007
PMID: 17641413
Small molecule inhibitors of the IGF-1R/IR axis for the treatment of cancer.
Buck E, Mulvihill M., Expert Opin Investig Drugs 20(5), 2011
PMID: 21446886
Simultaneous production of IGF-I and EGF competing growth factors by HT-29 human colon cancer line.
Culouscou JM, Remacle-Bonnet M, Garrouste F, Marvaldi J, Pommier G., Int. J. Cancer 40(5), 1987
PMID: 3500134
Opposing function of the proprotein convertases furin and PACE4 on breast cancer cells' malignant phenotypes: role of tissue inhibitors of metalloproteinase-1.
Lapierre M, Siegfried G, Scamuffa N, Bontemps Y, Calvo F, Seidah NG, Khatib AM., Cancer Res. 67(19), 2007
PMID: 17909005
Proprotein convertases: "master switches" in the regulation of tumor growth and progression.
Bassi DE, Fu J, Lopez de Cicco R, Klein-Szanto AJ., Mol. Carcinog. 44(3), 2005
PMID: 16167351
Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer.
Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J., Mol. Ther. 20(3), 2012
PMID: 22186789
Inhibition of the proprotein convertases represses the invasiveness of human primary melanoma cells with altered p53, CDKN2A and N-Ras genes.
Lalou C, Scamuffa N, Mourah S, Plassa F, Podgorniak MP, Soufir N, Dumaz N, Calvo F, Basset-Seguin N, Khatib AM., PLoS ONE 5(4), 2010
PMID: 20404912

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