HSF1: Primary Factor in Molecular Chaperone Expression and a Major Contributor to Cancer Morbidity

GUERRERO-GIMENEZ, MARTIN E.; CALDERWOOD, STUART K.; PRINCE, THOMAS L.; FERNANDEZ-MUÑOZ, JUAN MANUEL; LANG, BENJAMIN J.; ACKERMAN, ANDREW

Cells

MDPI

Lugar: Basel; Año: 2020 vol. 9

Heat shock factor 1 (HSF1) is the primary component for initiation of the powerful heat shockresponse (HSR) in eukaryotes. The HSR is an evolutionarily conserved mechanism for responding toproteotoxic stress and involves the rapid expression of heat shock protein (HSP) molecular chaperonesthat promote cell viability by facilitating proteostasis. HSF1 activity is amplified in many tumorcontexts in a manner that resembles a chronic state of stress, characterized by high levels of HSPgene expression as well as HSF1-mediated non-HSP gene regulation. HSF1 and its gene targets areessential for tumorigenesis across several experimental tumor models, and facilitate metastatic andresistant properties within cancer cells. Recent studies have suggested the significant potential ofHSF1 as a therapeutic target and have motivated research eorts to understand the mechanisms ofHSF1 regulation and develop methods for pharmacological intervention. We review what is currentlyknown regarding the contribution of HSF1 activity to cancer pathology, its regulation and expressionacross human cancers, and strategies to target HSF1 for cancer therapy.