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Published on: March 8, 2017
Calcium-sensing receptor modulates cell adhesion and migration via integrins
Sujeenthar Tharmalingam1, Avais M Daulat, Jordan E Antflick
1Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada.
The calcium-sensing receptor (CaSR) promotes tumor cell adhesion and migration by interacting with integrins. This ion-sensing receptor
Area of Science:
- Cellular Biology
- Molecular Biology
- Endocrinology
Background:
- The calcium-sensing receptor (CaSR) is a G protein-coupled receptor activated by extracellular divalent cations.
- CaSR regulates parathyroid hormone and calcitonin release in the endocrine system.
- CaSR's role in cellular adhesion and migration, particularly in cancer, is not well understood.
Purpose of the Study:
- To investigate the role of CaSR in cellular adhesion and migration in medullary thyroid carcinoma cells.
- To elucidate the molecular mechanisms linking CaSR to cellular adhesion and migration pathways.
Main Methods:
- Immunopurification, mass spectrometry, co-immunoprecipitation, and co-localization studies.
- Fibronectin-based cell adhesion and migration assays using CaSR modulators.
- Integrin inhibition studies and β1 knockdown experiments.
- Analysis of intracellular signaling pathways, including phospholipase C activation.
Main Results:
- CaSR forms a macromolecular complex with β1-containing integrins.
- CaSR activation promotes cell adhesion and migration, mediated by integrins.
- CaSR-induced effects involve phospholipase C activation and intracellular calcium release.
Conclusions:
- This study demonstrates the first functional coupling between an ion-sensing G protein-coupled receptor (CaSR) and integrins.
- CaSR and integrin interaction promotes tumor cell adhesion and migration, involving intracellular calcium signaling.
- The CaSR-integrin axis has implications for cancer metastasis, axonal growth, and stem cell attachment.
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