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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F16%3A10322647" target="_blank" >RIV/00064165:_____/16:10322647 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/16:10322647

Result on the web

<a href="http://dx.doi.org/10.1038/cddis.2015.389" target="_blank" >http://dx.doi.org/10.1038/cddis.2015.389</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/cddis.2015.389" target="_blank" >10.1038/cddis.2015.389</a>

Result language

angličtina

Original language name

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

Original language description

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. Delta NGLI2 (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 revealed a correlation between the tissue regions showing high GLI2 and survivin positivity. Thus, these results demonstrated that survivin is a classical transcriptional target of GLI2, a Hedgehog pathway signaling effector. This potentially reflects the high expression of survivin in human tumor cells. As the Hedgehog pathway is upregulated in virtually all types of cancer cells, these findings substantially contribute to the explanation of uniform survivin expression in tumors as a potential target for the development of a more effective treatment of cancers through the inhibition of GLI2 to restrain survivin activity.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

—

Project

<a href="/en/project/NT14005" target="_blank" >NT14005: Hedgehog-GLI signalling: an indicator of the tumor biological behavior in melanoma, lung cancer and some other tumors and its blocking as an antitumor therapy</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Cell death &amp; disease

ISSN

2041-4889

e-ISSN

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Volume of the periodical

7

Issue of the periodical within the volume

Neuveden

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

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UT code for WoS article

000369181000011

EID of the result in the Scopus database

2-s2.0-84955117709