HSF1: Guardian of Proteostasis in Cancer

Trends Cell Biol. 2016 Jan;26(1):17-28. doi: 10.1016/j.tcb.2015.10.011. Epub 2015 Nov 18.

Abstract

Proteomic instability is causally related to human diseases. In guarding proteome stability, the heat shock factor 1 (HSF1)-mediated proteotoxic stress response plays a pivotal role. Contrasting with its beneficial role of enhancing cell survival, recent findings have revealed a compelling pro-oncogenic role for HSF1. However, the mechanisms underlying the persistent activation and function of HSF1 within malignancy remain poorly understood. Emerging evidence reveals that oncogenic signaling mobilizes HSF1 and that cancer cells rely on HSF1 to avert proteomic instability and repress tumor-suppressive amyloidogenesis. In aggregate, these new developments suggest that cancer cells endure chronic proteotoxic stress and that proteomic instability is intrinsically associated with the malignant state, a characteristic that could be exploited to combat cancer.

Keywords: HSF1; amyloidogenesis; proteome homeostasis; proteotoxic stress; tumor suppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / physiology*
  • Heat Shock Transcription Factors
  • Homeostasis*
  • Humans
  • Neoplasms / metabolism*
  • Protein Processing, Post-Translational
  • Proteome / metabolism*
  • Signal Transduction
  • Transcription Factors / physiology*

Substances

  • DNA-Binding Proteins
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Proteome
  • Transcription Factors