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Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential
INSERM U866, Dijon, France
Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon, France
CNRS, UMR7216 Epigenetics and Cell Fate, Paris, France
University Paris Diderot, 75013 Paris, France
CHU, Dijon BP1542, Dijon, France
These two authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 30 January 2011 / Accepted: 23 February 2011 / Published: 7 March 2011
Abstract: Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.
Keywords: Heat Shock Factors; cancer; therapeutical approaches
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MDPI and ACS Style
De Thonel, A.; Mezger, V.; Garrido, C. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential. Cancers 2011, 3, 1158-1181.
De Thonel A, Mezger V, Garrido C. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential. Cancers. 2011; 3(1):1158-1181.
De Thonel, Aurelie; Mezger, Valerie; Garrido, Carmen. 2011. "Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential." Cancers 3, no. 1: 1158-1181.