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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Main Authors: Tingting Zhang, Ningning Li, Chaoyang Sun, Yang Jin, Xia Sheng
Format: Article
Language:English
Published: Springer Nature 2020-04-01
Series:EMBO Molecular Medicine
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Online Access:https://doi.org/10.15252/emmm.201911845
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author Tingting Zhang
Ningning Li
Chaoyang Sun
Yang Jin
Xia Sheng
author_facet Tingting Zhang
Ningning Li
Chaoyang Sun
Yang Jin
Xia Sheng
author_sort Tingting Zhang
collection DOAJ
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.
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institution Kabale University
issn 1757-4676
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language English
publishDate 2020-04-01
publisher Springer Nature
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series EMBO Molecular Medicine
spelling doaj-art-64152257da8948adae875c55d907fbc62025-08-20T03:46:19ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842020-04-0112511210.15252/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 TechnologyThe Seventh Affiliated Hospital of Sun Yat‐sen UniversityDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute for Cancer Genetics and Informatics, Oslo University HospitalMinistry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and TechnologyAbstract 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
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
title 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_short 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
topic cancer
ER stress
MYC
synthetic lethality
UPR
url https://doi.org/10.15252/emmm.201911845
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