Calcium Sensing Receptor Stimulates Breast Cancer Cell Migration Via the Gβγ-AKT-mTORC2 Signaling Pathway

Overview

Journal J Cell Commun Signal

Date 2021 Dec 2

PMID 34854057

Citations 5

Authors

Lennis Beatriz Orduna-Castillo

Jorge Eduardo Del-Rio-Robles

Irving Garcia-Jimenez

Cesar Zavala-Barrera

Yarely Mabell Beltran-Navarro

Joseline Janai Hidalgo-Moyle

Iliana Ramirez-Rangel

Marco A Hernandez-Bedolla

Alma P Reyes-Ibarra

Margarita Valadez-Sanchez

Jose Vazquez-Prado

Guadalupe Reyes-Cruz

Affiliations

Soon will be listed here.

Abstract

Calcium sensing receptor, a pleiotropic G protein coupled receptor, activates secretory pathways in cancer cells and putatively exacerbates their metastatic behavior. Here, we show that various CaSR mutants, identified in breast cancer patients, differ in their ability to stimulate Rac, a small Rho GTPase linked to cytoskeletal reorganization and cell protrusion, but are similarly active on the mitogenic ERK pathway. To investigate how CaSR activates Rac and drives cell migration, we used invasive MDA-MB-231 breast cancer cells. We revealed, by pharmacological and knockdown strategies, that CaSR activates Rac and cell migration via the Gβγ-PI3K-mTORC2 pathway. These findings further support current efforts to validate CaSR as a relevant therapeutic target in metastatic cancer.

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