内质网应激PERK通路在肿瘤中的研究进展

doi:10.11904/j.issn.1002-3070.2018.01.007

实用肿瘤学杂志 ›› 2018, Vol. 32 ›› Issue (1): 38-41.doi: 10.11904/j.issn.1002-3070.2018.01.007

内质网应激PERK通路在肿瘤中的研究进展

欧阳仲瑞¹, 柴双², 赵海杞¹ 综述, 刘耀华¹ 审校

1.哈尔滨医科大学附属第一医院神经外科(哈尔滨 150001);
2.内蒙古扎兰屯中蒙医院神经外科

收稿日期:2017-09-19 出版日期:2018-02-20 发布日期:2018-03-07
通讯作者: 刘耀华,E-mail:liuyaohua_harbin@hotmail.com
作者简介:欧阳仲瑞,男,(1990-),硕士研究生,从事胶质瘤基础与临床的研究。
基金资助:
国家自然科学基金(81372701)

Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor

OUYANG Zhongrui¹, CHAI Shuang², ZHAO Haiqi¹, LIU Yaohua¹

1.Department of Neurosurgery,First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;
2.Department of Neurosurgery,Zhalantun Traditional Chinese,Inn-Mongolia Medicine Hospital

Received:2017-09-19 Online:2018-02-20 Published:2018-03-07

摘要/Abstract

摘要： 肿瘤细胞在生长、浸润和转移过程中经历的缺氧、低糖等多种环境压力会对肿瘤细胞造成内质网应激,为应对内质网应激,肿瘤细胞会诱发未折叠蛋白反应(Unfolded protein response,UPR)。PERK通路作为激活UPR的一条关键通路可通过提高肿瘤对不良微环境的耐受程度、诱导新生血管生成、诱导自噬体形成、激活凋亡信号分子等促进肿瘤细胞生长、增殖、侵袭及保护性自噬,并且在UPR达到一定程度时诱导肿瘤细胞凋亡及自噬性死亡。

关键词: 内质网应激未折叠蛋白反应, 肿瘤细胞, PERK通路

Abstract: During growth,invasion and metastasis,tumor cells undergo endoplasmic reticulum stress(ERS)under hypoxia,hypoglycemia and other environmental stresses.In response to ERS,tumor cells induce unfolded protein response(UPR).PERK signaling pathway as a key pathway to activate UPR can promote survival,proliferation,invasion and protection of tumor cells by increasing tumor tolerance to adverse microenvironment,inducting angiogenesis,inducing autophagosome formation and activating apoptotic signal molecules.Tumor cells are induced apoptotic and autophagic death when UPR reaches a certain extent.

Key words: ERS, UPR, Tumor cells, PERK signaling pathway

中图分类号:

R730

欧阳仲瑞, 柴双, 赵海杞, 刘耀华. 内质网应激PERK通路在肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(1): 38-41.

OUYANG Zhongrui, CHAI Shuang, ZHAO Haiqi, LIU Yaohua. Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor[J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(1): 38-41.

参考文献

1 Cao SS,Kaufman RJ.Unfolded protein response[J].Curr Biol,2012,22(16):622-626.
2 Singleton DC,Harris AL.Targeting the ATF4 pathway in cancer therapy[J].Expert Opin Ther Targets,2012,16(12):1189-1202.
3 Koromilas AE.Roles of the translation initiation factor eIF2alpha serine 51 phosphorylation in cancer formation and treatment[J].Biochim Biophys Acta,2015,1849(7):871-880.
4 Bi M,Naczki C,Koritzinsky M,et al.ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth[J].EMBO J,2005,24(19):3470-3481.
5 Martinon F.Targeting endoplasmic reticulum signaling pathways in cancer[J].Acta Oncol,2012,51(7):822-830.
6 Zheng Q,Ye J,Cao J.Translational regulator eIF2alpha in tumor[J].Tumour Biol,2014,35(7):6255-6264.
7 胡亚玲.葡萄糖剥夺通过上调ATF4诱导结直肠癌耐药的实验研究[D].江苏:江南大学,2016.
8 Pyo CW,Choi JH,Oh SM,et al.Oxidative stress-induced cyclin D1 depletion and its role in cell cycle processing[J].Biochim Biophys Acta,2013,1830(11):5316-5325.
9 Han KS,Li N,Raven PA,et al.Inhibition of endoplasmic reticulum chaperone protein glucose-regulated protein 78 potentiates anti-angiogenic therapy in renal cell carcinoma through inactivation of the PERK/eIF2alpha pathway[J].Oncotarget,2015,6(33):34818-34830.
10 Chevet E,Hetz C,Samali A.Endoplasmic reticulum stress-activated cell reprogramming in oncogenesis[J].Cancer Discov,2015,5(6):586-597.
11 Dejeans N,Barroso K,Fernandez-Zapico ME,et al.Novel roles of the unfolded protein response in the control of tumor development and aggressiveness[J].Semin Cancer Biol,2015,33:67-73.
12 Manie SN,Lebeau J,Chevet E.Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease.3.orchestrating the unfolded protein response in oncogenesis:an update[J].Am J Physiol Cell Physiol,2014,307(10):901-907.
13 Sanda GM,Deleanu M,Toma L,et al.Oxidized LDL-exposed human macrophages display increased MMP-9 expression and secretion mediated by endoplasmic reticulum stress[J].J Cell Biochem,2017,118(4):661-669.
14 Feng YX,Sokol ES,Del Vecchio CA,et al.Epithelial-to-mesenchymal transition activates PERK-eIF2alpha and sensitizes cells to endoplasmic reticulum stress[J].Cancer Discov,2014,4(6):702-715.
15 Verfaillie T,Garg AD,Agostinis P.Targeting ER stress induced apoptosis and inflammation in cancer[J].Cancer Lett,2013,332(2):249-264.
16 Li Y,Guo Y,Tang J,et al.New insights into the roles of CHOP-induced apoptosis in ER stress[J].Acta Biochim Biophys Sin,2015,47(2):146-147.
17 李晓娟,夏榕蔓,楼招欢,等.丹参二萜醌通过PERK-EIF2α通路诱导肺癌PC9细胞凋亡的机制研究[J].中华中医药杂志,2017,32(5):1897-1902.
18 Hiramatsu N,Messah C,Han J,et al.Translational and posttranslational regulation of XIAP by eIF2alpha and ATF4 promotes ER stress-induced cell death during the unfolded protein response[J].Mol Biol Cell,2014,25(9):1411-1420.
19 Kroemer G,Marino G,Levine B.Autophagy and the integrated stress response[J].Mol Cell,2010,40(2):280-293.
20 Kania E,Pajak B,Orzechowski A.Calcium homeostasis and ER stress in control of autophagy in cancer cells[J].Biomed Res Int,2015,2015:1-12.
21 Kouroku Y,Fujita E,Tanida I,et al.ER stress(PERK/eIF2alpha phosphorylation)mediates the polyglutamine-induced LC3 conversion,an essential step for autophagy formation[J].Cell Death Differ,2007,14(2):230-239.
22 Hasanain M,Bhattacharjee A,Pandey P,et al.A-Solanine induces ROS-mediated autophagy through activation of endoplasmic reticulum stress and inhibition of Akt/mTOR pathway[J].Cell Death Dis,2015,6:e1860.
23 Hart LS,Cunningham JT,Datta T,et al.ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth[J].J Clin Invest,2012,122(12):4621-4634.
24 Suh DH,Kim MK,Kim HS,et al.Unfolded protein response to autophagy as a promising druggable target for anticancer therapy[J].Ann N Y Acad Sci,2012,1271:20-32.
25 Ma J,Yang YR,Chen W,et al.Fluoxetine synergizes with temozolomide to induce the CHOP-dependent endoplasmic reticulum stress-related apoptosis pathway in glioma cells[J].Oncol Rep,2016,36(2):676-684.
26 Atkins C,Liu Q,Minthorn E,et al.Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity[J].Cancer Res,2013,73(6):1993-2002.
27 Axten JM,Medina JR,Feng Y,et al.Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine(GSK2606414),a potent and selective first-in-class inhibitor of protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)[J].J Med Chem,2012,55(16):7193-207.
28 Nagelkerke A,BussinkJ,Van Der Kogel AJ,et al.The PERK/ATF4/LAMP3-arm of the unfolded protein response affects radioresistance by interfering with the DNA damage response[J].Radiother Oncol,2013,108(3):415-421.

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内质网应激PERK通路在肿瘤中的研究进展

Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor

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