Mutant p53 and cellular stress pathways: A criminal alliance that promotes cancer progression

Gabriella D’Orazi, Mara Cirone

Research output: Contribution to journalArticlepeer-review

Abstract

The capability of cancer cells to manage stress induced by hypoxia, nutrient shortage, acidosis, redox imbalance, loss of calcium homeostasis and exposure to drugs is a key factor to ensure cancer survival and chemoresistance. Among the protective mechanisms utilized by cancer cells to cope with stress a pivotal role is played by the activation of heat shock proteins (HSP) response, anti-oxidant response induced by nuclear factor erythroid 2-related factor 2 (NRF2), the hypoxia-inducible factor-1 (HIF-1), the unfolded protein response (UPR) and autophagy, cellular processes strictly interconnected. However, depending on the type, intensity or duration of cellular stress, the balance between pro-survival and pro-death pathways may change, and cell survival may be shifted into cell death. Mutations of p53 (mutp53), occurring in more than 50% of human cancers, may confer oncogenic gain-of-function (GOF) to the protein, mainly due to its stabilization and interaction with the above reported cellular pathways that help cancer cells to adapt to stress. This review will focus on the interplay of mutp53 with HSPs, NRF2, UPR, and autophagy and discuss how the manipulation of these interconnected processes may tip the balance towards cell death or survival, particularly in response to therapies.

Original languageEnglish
Article number614
JournalCancers
Volume11
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • Anticancer therapy
  • Antioxidant response
  • Autophagy
  • Endoplasmic reticulum (ER) stress
  • Gain-of-function (GOF)
  • Heat shock protein (HSP)
  • Hypoxia-inducible factor 1 (HIF-1)
  • Mutant p53 (mutp53)
  • Nuclear factor erythroid 2-related factor 2 (NRF2)
  • Unfolded protein response (UPR)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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