IP3R3 silencing induced actin cytoskeletal reorganization through ARHGAP18/RhoA/mDia1/FAK pathway in breast cancer cell lines.

Abstract

Cell morphology is altered in the migration process, and the underlying cytoskeleton remodeling is highly dependent of intracellular Ca2+ concentration. Many calcium channels are known to be involved in migration. Inositol 1,4,5-trisphosphate receptor (IP3R) was demonstrated to be implicated in breast cancer cells migration, but its involvement in morphological changes during the migration process remains unclear. In the present work, we showed that IP3R3 expression was correlated to cell morphology. IP3R3 silencing induced rounding shape and decreased adhesion in invasive breast cancer cell lines. Moreover, IP3R3 silencing decreased ARHGAP18 expression, RhoA activity, Cdc42 expression and Y861FAK phosphorylation. Interestingly, IP3R3 was able to regulate profilin remodeling, without inducing any myosin II reorganization. IP3R3 silencing revealed an oscillatory calcium signature, with a predominant oscillating profile occurring in early wound repair. To summarize, we demonstrated that IP3R3 is able to modulate intracellular Ca2+ availability and to coordinate the remodeling of profilin cytoskeleton organization through the ARHGAP18/RhoA/mDia1/FAK pathway.

• Authors: Alexia Vautrin-Glabik, Béatrice Botia, Philippe Kischel, Halima Ouadid-Ahidouch, Lise Rodat-Despoix
• Journal: Biochimica et biophysica acta. Molecular cell research (Biochim Biophys Acta Mol Cell Res) Vol. 1865 Issue 7 Pg. 945-958 (07 2018) ISSN: 0167-4889 [Print] Netherlands
• PMID: 29630900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• ARHGAP18 protein, human
• Adaptor Proteins, Signal Transducing
• DIAPH1 protein, human
• Formins
• GTPase-Activating Proteins
• ITPR3 protein, human
• Inositol 1,4,5-Trisphosphate Receptors
• Profilins
• RHOA protein, human
• Focal Adhesion Kinase 1
• PTK2 protein, human
• rhoA GTP-Binding Protein
• Calcium

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Breast Neoplasms (genetics, metabolism)
• Calcium (metabolism)
• Cell Adhesion
• Cell Line, Tumor
• Female
• Focal Adhesion Kinase 1 (metabolism)
• Formins
• GTPase-Activating Proteins (metabolism)
• Gene Silencing
• Humans
• Inositol 1,4,5-Trisphosphate Receptors (genetics, metabolism)
• MCF-7 Cells
• Phosphorylation
• Profilins (metabolism)
• Signal Transduction
• rhoA GTP-Binding Protein (metabolism)