Type III TGFβ receptor and Src direct hyaluronan-mediated invasive cell motility.

Allison P, Espiritu D, Barnett JV, Camenisch TD
Cell Signal. 2015 27 (3): 453-9

PMID: 25499979 · PMCID: PMC5604324 · DOI:10.1016/j.cellsig.2014.11.037

During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. This process requires epithelial to mesenchymal transition (EMT) and directed cellular invasion. The Type III Transforming Growth Factor-beta Receptor (TGFβR3) is required for epicardial cell invasion and coronary vessel development. Using primary epicardial cells derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, high-molecular weight hyaluronan (HMWHA) stimulated cellular invasion and filamentous (f-actin) polymerization are detected in Tgfbr3(+/+) cells, but not in Tgfbr3(-/-) cells. Furthermore, HMWHA-stimulated cellular invasion and f-actin polymerization in Tgfbr3(+/+) epicardial cells are dependent on Src kinase. Src activation in HMWHA-stimulated Tgfbr3(-/-) epicardial cells is not detected in response to HMWHA. RhoA and Rac1 also fail to activate in response to HMWHA in Tgfbr3(-/-) cells. These events coincide with defective f-actin formation and deficient cellular invasion. Finally, a T841A activating substitution in TGFβR3 drives ligand-independent Src activation. Collectively, these data define a TGFβR3-Src-RhoA/Rac1 pathway that is essential for hyaluronan-directed cell invasion in epicardial cells.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (21)

Actin Cytoskeleton Amino Acid Substitution Animals Arrestin cdc42 GTP-Binding Protein Cell Movement Cells, Cultured Epithelial-Mesenchymal Transition Hyaluronic Acid Mice Neuropeptides Pericardium Protein Binding Proteoglycans rac1 GTP-Binding Protein Receptors, Transforming Growth Factor beta rhoA GTP-Binding Protein rho GTP-Binding Proteins RNA, Small Interfering RNA Interference src-Family Kinases

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