| Literature DB >> 34854057 |
Lennis Beatriz Orduña-Castillo1, Jorge Eduardo Del-Río-Robles1, Irving García-Jiménez1, César Zavala-Barrera1, Yarely Mabell Beltrán-Navarro2, Joseline Janai Hidalgo-Moyle1, Iliana Ramírez-Rangel2, Marco A Hernández-Bedolla1,3, Alma P Reyes-Ibarra1, Margarita Valadez-Sánchez1, José Vázquez-Prado2, Guadalupe Reyes-Cruz4.
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.Entities:
Keywords: Breast cancer; Calcium sensing receptor; Cell migration; GPCR signaling; Rac-1 GTPase; mTORC2
Year: 2021 PMID： 34854057 PMCID： PMC8891408 DOI： 10.1007/s12079-021-00662-y
Source DB: PubMed Journal: J Cell Commun Signal ISSN： 1873-9601 Impact factor: 5.908