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

Lennis Beatriz Orduña-Castillo1, Jorge Eduardo Del-Río-Robles1, Irving García-Jiménez1

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

Journal of Cell Communication and Signaling
|December 2, 2021
PubMed

Insights

The calcium-sensing receptor (CaSR) in breast cancer cells activates Rac, a protein crucial for cell migration. This occurs through the Gβγ-PI3K-mTORC2 pathway, suggesting CaSR as a therapeutic target for metastatic cancer.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Oncology

Background:

  • The calcium-sensing receptor (CaSR) is a G protein-coupled receptor implicated in cancer cell signaling.
  • CaSR activation may promote cancer metastasis by influencing cellular pathways.

Purpose of the Study:

  • To investigate the role of CaSR mutants in breast cancer.
  • To elucidate the molecular mechanisms by which CaSR activates Rac and promotes cell migration.

Main Methods:

  • Utilized various CaSR mutants found in breast cancer patients.
  • Employed pharmacological inhibitors and knockdown strategies in MDA-MB-231 breast cancer cells.
  • Assessed Rac activation, ERK pathway activity, and cell migration.

Main Results:

  • CaSR mutants showed differential effects on Rac activation but similar activity on the ERK pathway.
  • CaSR-mediated Rac activation and cell migration were dependent on the Gβγ-PI3K-mTORC2 pathway.
  • Identified a novel signaling axis linking CaSR to cytoskeletal dynamics and cell motility.

Conclusions:

  • CaSR signaling, particularly through the Gβγ-PI3K-mTORC2 pathway, drives Rac activation and cell migration in invasive breast cancer.
  • These findings highlight the potential of targeting CaSR for the treatment of metastatic breast cancer.
Keywords:
Breast cancerCalcium sensing receptorCell migrationGPCR signalingRac-1 GTPasemTORC2

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