Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.
Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.
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解开GPCRs、ERS和EMT之间的分子联系。
DOI：
10.1155/2021/6655417
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发表时间：
2021
影响因子：
4.6
通讯作者：
North BJ
中科院分区：
文献类型：
--
作者：
Kumari N;Reabroi S;North BJ
G蛋白偶联受体(GPCRs)是一大类跨膜蛋白，可将外界刺激转化为多种细胞反应。它们通过调节肿瘤形成和进展中的一些关键过程，在包括癌症在内的人类各种病理条件下发挥关键作用。上皮-间充质转化(EMT)是促进癌细胞侵袭和肿瘤扩散导致转移的基本过程，通常是一种难以治愈的疾病状态。癌细胞的不受控制的增殖和持续的新陈代谢也会导致氧化应激、缺氧和生长因子和营养物质的枯竭。这些干扰导致错误折叠的蛋白质在内质网(ER)中积累，并诱导一种称为内质网应激(ERS)的细胞状况，而未折叠蛋白反应(UPR)的激活可抵消这种应激。许多GPCRs通过ERS传感器、IRE1α、PERK和ATF6来调节ERS和UPR信号，以支持癌细胞存活和抑制细胞死亡。GPCRs通过调节下游信号通路，如核因子-κB、丝裂原活化蛋白K/ERK、PI3K/AkT、转化生长因子-β和WNT/β-连环蛋白，还上调间充质转录因子，包括Snail、ZeB和Twist超家族，调节细胞极性、细胞骨架重塑、迁移和侵袭。同样，ERS诱导的UPR上调与EMT相关的基因转录和蛋白表达，从而增强肿瘤的侵袭性。尽管GPCRs在癌症生物学中是有吸引力的治疗靶点，但人们对它们在调节ERS和EMT中的作用知之甚少。在这里，我们将讨论GPCR-ERS与癌细胞EMT过程的相互作用，特别关注癌基因和分子信号通路。
G protein-coupled receptors (GPCRs) represent a large family of transmembrane proteins that transduce an external stimulus into a variety of cellular responses. They play a critical role in various pathological conditions in humans, including cancer, by regulating a number of key processes involved in tumor formation and progression. The epithelial-mesenchymal transition (EMT) is a fundamental process in promoting cancer cell invasion and tumor dissemination leading to metastasis, an often intractable state of the disease. Uncontrolled proliferation and persistent metabolism of cancer cells also induce oxidative stress, hypoxia, and depletion of growth factors and nutrients. These disturbances lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and induce a cellular condition called ER stress (ERS) which is counteracted by activation of the unfolded protein response (UPR). Many GPCRs modulate ERS and UPR signaling via ERS sensors, IRE1α, PERK, and ATF6, to support cancer cell survival and inhibit cell death. By regulating downstream signaling pathways such as NF-κB, MAPK/ERK, PI3K/AKT, TGF-β, and Wnt/β-catenin, GPCRs also upregulate mesenchymal transcription factors including Snail, ZEB, and Twist superfamilies which regulate cell polarity, cytoskeleton remodeling, migration, and invasion. Likewise, ERS-induced UPR upregulates gene transcription and expression of proteins related to EMT enhancing tumor aggressiveness. Though GPCRs are attractive therapeutic targets in cancer biology, much less is known about their roles in regulating ERS and EMT. Here, we will discuss the interplay in GPCR-ERS linked to the EMT process of cancer cells, with a particular focus on oncogenes and molecular signaling pathways.
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DOI：
10.12659/msm.908176
发表时间：
2018-05-28
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Che X;Zhang G;Zhang X;Xue J
通讯作者：
Xue J
影响因子：
--
作者：
Andradas C;Blasco-Benito S;Castillo-Lluva S;Dillenburg-Pilla P;Diez-Alarcia R;Juanes-García A;García-Taboada E;Hernando-Llorente R;Soriano J;Hamann S;Wenners A;Alkatout I;Klapper W;Rocken C;Bauer M;Arnold N;Quintanilla M;Megías D;Vicente-Manzanares M;Urigüen L;Gutkind JS;Guzmán M;Pérez-Gómez E;Sánchez C
通讯作者：
Sánchez C
影响因子：
6.4
作者：
Chan, Yu-Tzu;Lai, Alan C. -Y.;Yu, Alice L.
通讯作者：
Yu, Alice L.
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG
影响因子：
7.2
作者：
Braakman, Ineke;Hebert, Daniel N.
通讯作者：
Hebert, Daniel N.