Fig. 4

The many effects of HSF1 in cancer. HSF1 plays diverse roles in tumorigenesis by modulating various cellular processes. It drives metabolic reprogramming in cancer cells, aiding the shift to aerobic glycolysis [116, 117]. HSF1 also promotes tumor survival by preventing cell death by altering the levels of various pro- and anti-apoptotic proteins [118,119,120,121]. It is also known for indirectly stabilizing oncogenic signaling pathways– for example, the MAPK/ERK cascade, which regulates KSR1, a key scaffolding protein required for proper pathway activation [92]. Additionally, phosphorylation of HSF1 at serine 326 is associated with epithelial-to-mesenchymal transition (EMT), and enhanced tumor invasiveness [113]. Beyond cancer cells, HSF1 can influence the tumor microenvironment (TME) by reprogramming natural killer (NK) cells, leading to reduced cytotoxicity against tumor cells [122]. Furthermore, HSF1 expression in cancer-associated fibroblasts (CAFs) contributes to tumor progression through the secretion of extracellular vesicles (EVs) containing pro-tumorigenic factors such as inhibin β-A and thrombospondin 2 [123]. These diverse functions establish HSF1 as a central and complex regulator of cancer progression