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Dadun > Depósito Académico > Facultad de Ciencias > Departamento de Histología y Anatomía Patológica > DA - Ciencias - HAP - Artículos de revista >

The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression
Authors: Ezponda, T. (T.)
Pajares, M.J. (María José)
Agorreta, J. (Jackeline)
Echeveste, J.I. (José I.)
Lopez-Picazo, J.M. (José M.)
Torre, W. (Wenceslao)
Pio, R. (Rubén)
Montuenga, L.M. (Luis M.)
Keywords: The Oncoprotein SF2/ASF
Promotes Non–Small
Cell Lung Cancer
Survival
Enhancing
Survivin Expression
Issue Date: 3-Aug-2010
Publisher: American Association for Cancer Research
Publisher version: http://dx.doi.org/10.1158/1078-0432.CCR-10-0076
ISSN: 1078-0432
Citation: Ezponda T, Pajares MJ, Agorreta J, Echeveste JI, Lopez-Picazo JM, Torre W, et al. The oncoprotein SF2/ASF promotes non-small cell lung cancer survival by enhancing survivin expression. Clin Cancer Res 2010 Aug 15;16(16):4113-4125.
Abstract
Abstract Purpose: SF2/ASF is a splicing factor recently described as an oncoprotein. In the present work, we examined the role of SF2/ASF in human non–small cell lung cancer (NSCLC) and analyzed the molecular mechanisms involved in SF2/ASF-related carcinogenesis. Experimental Design: SF2/ASF protein levels were analyzed in 81 NSCLC patients by immunohistochemistry. SF2/ASF downregulation cellular models were generated using small interfering RNAs, and the effects on proliferation and apoptosis were evaluated. Survivin and SF2/ASF expression in lung tumors was analyzed by Western blot and immunohistochemistry. Survival curves and log-rank test were used to identify the association between the expression of the proteins and time to progression. Results: Overexpression of SF2/ASF was found in most human primary NSCLC tumors. In vitro downregulation of SF2/ASF induced apoptosis in NSCLC cell lines. This effect was associated with a reduction in the expression of survivin, an antiapoptotic protein widely upregulated in cancer. In fact, SF2/ASF specifically bound survivin mRNA and enhanced its translation, via a mammalian target of rapamycin complex 1 (mTORC1) pathway-dependent mechanism, through the phosphorylation and inactivation of the translational repressor 4E-BP1. Moreover, SF2/ASF promoted the stability of survivin mRNA. A strong correlation was observed between the expression of SF2/ASF and survivin in tumor biopsies from NSCLC patients, supporting the concept that survivin expression levels are controlled by SF2/ASF. Furthermore, combined expression of these proteins was associated with prognosis. Conclusion: This study provides novel data on the mTORC1- and survivin-dependent mechanisms of SF2/ASF-related carcinogenic potential, and shows that SF2/ASF and survivin expression is involved in NSCLC progression.
Permanent link: http://hdl.handle.net/10171/12900
Appears in Collections:DA - CIMA - Oncología - Biomarcadores - Artículos de Revista
DA - Ciencias - HAP - Artículos de revista

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