GPER induces mitochondrial fission through p44/42 MAPK-Drp1 pathway in breast cancer cells

被引：9

作者：

Rekha, Pothuganti ^{[1
]}

Gupta, Anshu ^{[1
]}

Goud, Kalali Sridivya ^{[1
]}

Biswas, Bidisha ^{[1
]}

Bhattar, Subhashith ^{[1
]}

Vijayakumar, Gangipangi ^{[1
]}

Selvaraju, Sudhagar ^{[1
]}

机构：

[1] Natl Inst Pharmaceut Educ & Res, Dept Biotechnol, Gauhati 781101, Assam, India

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2023年 / 643卷

关键词：

GPER; Mitochondrial dynamics; MAPK; Drp-1; Breast cancer; FUSION; DRP1; PHOSPHORYLATION; TARGET;

D O I：

10.1016/j.bbrc.2022.12.061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Understanding GPER biology in breast cancer is rather limited in compassion to the classic estrogen receptors. Mitochondrial dynamics play a critical role in determining cell survival and death under various microenvironmental conditions. We present evidence that GPER-induce mitochondrial fission in breast cancer cells. GPER mediated mitochondrial fission through activating Drp1 by phosphorylating S616 residue and down-regulates fusion proteins Mfn1 and Mfn2 levels. GPER-induced Drp1 activation mediated by p44/42 MAPK and inhibition of this signalling axis completely reverse the mitochondrial fission induced by GPER. Further, mitochondrial fission is required for GPER-induced cell death in breast cancer cells. To conclude, GPER induces mitochondrial fission through p44/42 MAPK -Drp1 signalling, and mitochondrial fission is critical for GPER-induced cell death in breast cancer cells. General significance: First time we report GPER's role in mitochondrial dynamics in cancer cells. Mito-chondrial dynamics play a critical role in cancer progression including tamoxifen resistance. Exploring a detailed mechanistic understanding of GPER signalling may help to design new therapy for advanced cancers. (c) 2022 Elsevier Inc. All rights reserved.

引用

页码：16 / 23

页数：8

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