Pleiotropic Role of HSF1 in Neoplastic Transformation
Natalia Vydra, Agnieszka Toma and Wieslawa Widlak
Affiliation: Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101 Gliwice, Poland.
Keywords: Cancer, drug resistance, genomic instability, HSF1 inhibitors, HSPs, metastasis, p53 signaling.
HSF1 (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. HSF1 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 HSF1 supports tumor
initiation and growth, as well as metastasis and angiogenesis. It also modulates the sensitivity of cancer cells to therapy.
Functions of HSF1 in cancer are connected with HSPs’ activity, which generally protects cells from apoptosis, but also
are independent of its classical targets. HSF1-dependent regulation of non-HSPs genes plays a role in cell cycle
progression, glucose metabolism, autophagy and drug efflux. HSF1 affects the key cell-survival and regulatory pathways,
including p53, RAS/MAPK, cAMP/PKA, mTOR and insulin signaling. Although the exact mechanism of HSF1 action is
still somewhat obscure, HSF1 is becoming an attractive target in anticancer therapies, whose inhibition could enhance the
effects of other treatments.
Rights & PermissionsPrintExport