Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway.
Lennis Beatriz Orduña-CastilloJorge Eduardo Del-Río-RoblesIrving García-JiménezCésar Zavala-BarreraYarely Mabell Beltrán-NavarroJoseline Janai Hidalgo-MoyleIliana Ramírez-RangelMarco A Hernández-BedollaAlma P Reyes-IbarraMargarita Valadez-SánchezJosé Vázquez-PradoGuadalupe Reyes-CruzPublished in: Journal of cell communication and signaling (2021)
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.
Keyphrases
- cell migration
- signaling pathway
- breast cancer cells
- pi k akt
- squamous cell carcinoma
- small cell lung cancer
- cell proliferation
- epithelial mesenchymal transition
- papillary thyroid
- induced apoptosis
- single cell
- cell therapy
- quality improvement
- childhood cancer
- protein kinase
- lymph node metastasis
- mesenchymal stem cells
- bone marrow