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Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway

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Journal of Cell Communication and Signaling Aims and scope

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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Acknowledgements

We acknowledge the technical assistance provided by Estanislao Escobar-Islas, Jaime Estrada-Trejo, Israel Valencia-Martínez and David Pérez. The authors express their gratitude to Maggie Brunner, MA, for editorial/style corrections. The authors declare no conflict of interest. This work was supported by grants from CONACyT (240119 and CF-2019-1794 to G.R.C.) and (286274 to J.V.P.), Fondo Sep-CINVESTAV (FidSC2018/3 to G.R.C.). L.B. O-C, J.E. del-R-R, I. G-J, C. Z-B, Y.M. B-N, J. J. H-M, I. R-R, M.A, H-B; and A.P. R-I are and were graduate students supported by CONACyT fellowships. The authors declare that there are no competing interests associated with the manuscript.

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  1. Marco A. Hernández-Bedolla

    Present address: Licenciatura en Enfermería, Escuela Superior de Huejutla, Universidad Autónoma del Estado de Hidalgo, Huejutla de Reyes, Hidalgo, México

Authors and Affiliations

  1. Department of Cell Biology, CINVESTAV, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, CP 07360, Mexico City, Mexico

    Lennis Beatriz Orduña-Castillo, Jorge Eduardo del-Río-Robles, Irving García-Jiménez, César Zavala-Barrera, Joseline Janai Hidalgo-Moyle, Marco A. Hernández-Bedolla, Alma P. Reyes-Ibarra, Margarita Valadez-Sánchez & Guadalupe Reyes-Cruz

  2. Department Pharmacology, CINVESTAV-IPN, Mexico City, Mexico

    Yarely Mabell Beltrán-Navarro, Iliana Ramírez-Rangel & José Vázquez-Prado

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  1. Lennis Beatriz Orduña-Castillo
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Contributions

Conceived and designed the experiments: L.B. O-C; J.E. del-R-R; I. R-R; J.V.P., and G.R.C. Supervised the study: G.R.C. Performed the experiments: L.B. O-C; J.E. del-R-R; C. Z-B; I. G-J; I. R-R; M.A. H-B; A.P. R-I, J. J.H-M, and M.V-S. Performed data mining: Y.M. B-N. Analyzed the data: L.B. O-C; J.E. del-R-R; C. Z-B; I.G-J; I.R-R, and M.A.H-B. Wrote the paper: L.B. O-C; J.V.P. and G.R.C. All authors reviewed and approved the final manuscript.

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Correspondence to Guadalupe Reyes-Cruz.

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Orduña-Castillo, L.B., del-Río-Robles, J.E., García-Jiménez, I. et al. Calcium sensing receptor stimulates breast cancer cell migration via the Gβγ-AKT-mTORC2 signaling pathway. J. Cell Commun. Signal. 16, 239–252 (2022). https://doi.org/10.1007/s12079-021-00662-y

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