MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?

Abstract:

:The transcription factors of the MYC family play pivotal roles in the initiation and progression of human cancers. High oncogenic level of MYC invades low-affinity sites and enhancer sequences, which subsequently alters the transcriptome, causes metabolic imbalance, and induces stress response. The endoplasmic reticulum (ER) not only plays a central role in maintaining proteostasis, but also contributes to other key biological processes, including Ca2+ metabolism and the synthesis of lipids and glucose. Stress conditions, such as shortage in glucose or oxygen and disruption of Ca2+ homeostasis, may perturb proteostasis and induce the unfolded protein response (UPR), which either restores homeostasis or triggers cell death. Crucial roles of ER stress and UPR signaling have been implicated in various cancers, from oncogenesis to treatment response. Here, we summarize the current knowledge on the interaction between MYC and UPR signaling, and its contribution to cancer development. We also discuss the potential of targeting key UPR signaling nodes as novel synthetic lethal strategies in MYC-driven cancers.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Zhang T,Li N,Sun C,Jin Y,Sheng X

doi

10.15252/emmm.201911845

subject

Has Abstract

pub_date

2020-05-08 00:00:00

pages

e11845

issue

5

eissn

1757-4676

issn

1757-4684

journal_volume

12

pub_type

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