PERK Integrates Oncogenic Signaling and Cell Survival During Cancer Development.
PERK Integrates Oncogenic Signaling and Cell Survival During Cancer Development.
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DOI：
10.1002/jcp.25336
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发表时间：
2016-10
影响因子：
5.6
通讯作者：
Diehl JA
中科院分区：
文献类型：
--
作者：
Bu Y;Diehl JA
未折叠蛋白应答（Unfolded protein responses，UPR）由三个主要的转导子PERK、IRE 1和ATF 6组成，在各种细胞内和细胞外挑战中发生，这些挑战扰乱了内质网（内质网）中的蛋白折叠。ER应激发生并且被认为是许多人类疾病的促成因素，包括癌症、神经退行性疾病和各种代谢综合征。在肿瘤生长的背景下，由癌基因如c-Myc、BrafV 600 E和HRASG 12 V的失调引起的致癌应激触发UPR作为癌细胞存活的适应性策略。PERK是一种ER驻留I型蛋白激酶，具有促凋亡和促存活能力。PERK，作为一个协调器，通过其下游底物，重新编程癌症基因表达，以促进生存的癌基因和微环境的挑战，如缺氧，血管生成和转移。在本文中，我们讨论了PERK激酶如何参与肿瘤的起始，转化，适应微环境应激，化学抗性以及PERK靶向治疗的潜在机会和潜在机会。
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, BrafV600E and HRASG12V 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.