Survivin, a novel target of the Hedgehog/GLI signaling pathway in human tumor cells

Cell Death & Disease
K VlčkováP Poučková

Abstract

Survivin, an important antiapoptotic protein, is expressed in tumors, whereas in normal tissues the expression of this protein is extremely low, defining a role for survivin as a cancer gene. Survivin exhibits multifunctional activity in tumor cells. However, why survivin expression is sharply and invariably restricted to tumor tissue remains unclear. Here, we identified 11 putative consensus binding sites for GLI transcription factors in the survivin promoter and characterized the promoter activity. Inhibitors of the Hedgehog/GLI pathway, cyclopamine and GANT61, decreased the promoter activity in reporter assays. ΔNGLI2 (which lacks the repressor domain) was the most potent vector in activating the survivin promoter-reporter. Moreover, GANT61, a GLI1/2 inhibitor, repressed endogenous survivin protein and mRNA expression in most cells across a large panel of tumor cell lines. Chromatin immunoprecipitation showed GLI2 binding to the survivin promoter. The ectopic GLI2-evoked expression of endogenous survivin was observed in normal human fibroblasts. GANT61 decreased survivin level in nude mice tumors, mimicking the activity of GANT61 in cultured cells. The immunohistochemistry and double immunofluorescence of human tumors reveal...Continue Reading

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Citations

Feb 2, 2017·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Yoshikazu KoikeJunichi Kurebayashi
May 8, 2018·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Davide SchifferLaura Annovazzi
Oct 19, 2017·International Journal of Oncology·Petar OzretićMaja Sabol
Aug 31, 2016·International Journal of Oncology·Kateřina VlčkováJiri Vachtenheim
Aug 26, 2018·International Journal of Molecular Sciences·Stephanie HehlgansShahram Ghanaati
Nov 14, 2018·Medicinal Research Reviews·David Martínez-GarcíaVanessa Soto-Cerrato
Sep 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Rajesh KotcherlakotaVijaya Gopal

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Methods Mentioned

BETA
PCR
immunoprecipitation assay
FCS
electrophoresis
transfections
transfection
immunoprecipitation

Software Mentioned

FIJI

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