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 respo...
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doaj-64152257da8948adae875c55d907fbc62021-08-02T11:26:49ZengWileyEMBO Molecular Medicine1757-46761757-46842020-05-01125n/an/a10.15252/emmm.201911845MYC and the unfolded protein response in cancer: synthetic lethal partners in crime?Tingting Zhang0Ningning Li1Chaoyang Sun2Yang Jin3Xia Sheng4Ministry of Education Key Lab of Environment and Health School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaThe Seventh Affiliated Hospital of Sun Yat‐sen University Shenzhen ChinaDepartment of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaInstitute for Cancer Genetics and Informatics Oslo University Hospital Oslo NorwayMinistry of Education Key Lab of Environment and Health School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract 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.https://doi.org/10.15252/emmm.201911845cancerER stressMYCsynthetic lethalityUPR |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tingting Zhang Ningning Li Chaoyang Sun Yang Jin Xia Sheng |
spellingShingle |
Tingting Zhang Ningning Li Chaoyang Sun Yang Jin Xia Sheng MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? EMBO Molecular Medicine cancer ER stress MYC synthetic lethality UPR |
author_facet |
Tingting Zhang Ningning Li Chaoyang Sun Yang Jin Xia Sheng |
author_sort |
Tingting Zhang |
title |
MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? |
title_short |
MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? |
title_full |
MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? |
title_fullStr |
MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? |
title_full_unstemmed |
MYC and the unfolded protein response in cancer: synthetic lethal partners in crime? |
title_sort |
myc and the unfolded protein response in cancer: synthetic lethal partners in crime? |
publisher |
Wiley |
series |
EMBO Molecular Medicine |
issn |
1757-4676 1757-4684 |
publishDate |
2020-05-01 |
description |
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. |
topic |
cancer ER stress MYC synthetic lethality UPR |
url |
https://doi.org/10.15252/emmm.201911845 |
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1721233105574952960 |