Pleiotropic Role of HSF in Neoplastic Transformation.

Pleiotropic Role of HSF in Neoplastic Transformation. Curr Cancer Drug Targets. 2014 Jan 22; Authors: Vydra N, Toma A, Widlak W Abstract HSF (Heat Shock transcription Factor 1) is the main transcription factor activated in response to proteotoxic stress. Once activated, it induces an expression of heat shock proteins (HSPs) which enables cells to survive in suboptimal conditions. HSF could be also activated by altered kinase signaling characteristic for cancer cells, which is a probable reason for its high activity found in a broad range of tumors. There is rapidly growing evidence that HSF supports tumor initiation and growth, as well as metastasis and angiogenesis. It also modulates the sensitivity of cancer cells to therapy. Functions of HSF in cancer are connected with HSPs' activity, which generally protects cells from apoptosis, but also are independent of its classical targets. HSF-dependent regulation of non-HSPs genes plays a role in cell cycle progression, glucose metabolism, autophagy and drug efflux. HSF affects the key cell-survival and regulatory pathways, including p53, RAS/MAPK, cAMP/PKA, mTOR and insulin signaling. Although the exact mechanism of HSF action is still somewhat obscure, HSF is becoming an attractive target in anticancer therapies, whose inhibition could enhance the effects of other treatments. PMID: 24467529 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research