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PERK Integrates Oncogenic Signaling and Cell Survival During Cancer Development
Author(s) -
Bu Yiwen,
Diehl J. Alan
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25336
Subject(s) - atf6 , unfolded protein response , cancer research , endoplasmic reticulum , biology , cancer , cancer cell , context (archaeology) , kinase , angiogenesis , microbiology and biotechnology , genetics , paleontology
Unfolded protein responses (UPR), consisting of three major transducers PERK, IRE1, and ATF6, occur in the midst of a variety of intracellular and extracellular challenges that perturb protein folding in the endoplasmic reticulum (ER). ER stress occurs and is thought to be a contributing factor to a number of human diseases, including cancer, neurodegenerative disorders, and various metabolic syndromes. In the context of neoplastic growth, oncogenic stress resulting from dysregulation of oncogenes such as c‐Myc, Braf V600E , and HRAS G12V trigger the UPR as an adaptive strategy for cancer cell survival. PERK is an ER resident type I protein kinase harboring both pro‐apoptotic and pro‐survival capabilities. PERK, as a coordinator through its downstream substrates, reprograms cancer gene expression to facilitate survival in response to oncogenes and microenvironmental challenges, such as hypoxia, angiogenesis, and metastasis. Herein, we discuss how PERK kinase engages in tumor initiation, transformation, adaption microenvironmental stress, chemoresistance and potential opportunities, and potential opportunities for PERK targeted therapy. J. Cell. Physiol. 231: 2088–2096, 2016. © 2016 Wiley Periodicals, Inc.