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

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. Mitochondrial 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. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Pothuganti Rekha, Anshu Gupta, Kalali Sridivya Goud, Bidisha Biswas, Subhashith Bhattar, Gangipangi Vijayakumar, Sudhagar Selvaraju. GPER induces mitochondrial fission through p44/42 MAPK - Drp1 pathway in breast cancer cells. Biochemical and biophysical research communications. 2023 Feb 05;643:16-23

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PMID: 36584588

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