A novel role for p115RhoGEF in regulation of epithelial plasticity.
Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module.
Department of Pharmacology and Experimental Therapeutics, LSU Health Sciences Center, New Orleans, Louisiana, United States of America.
Swapnil S
SS
Kher
Stanley S. Scott Cancer Center, LSU Health Sciences Center, New Orleans, Louisiana, United States of America.
Amanda P
AP
Struckhoff
Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, United States of America.
Arthur S
AS
Alberts
Department of Oral Biology, LSU Health Sciences Center, New Orleans, Louisiana, United States of America.
Rebecca A
RA
Worthylake
D022005:Adherens Junctions / Q000378:metabolism; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002465:Cell Movement; D004847:Epithelial Cells / Q000502:physiology*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D064067:Rho Guanine Nucleotide Exchange Factors / Q000502:physiology
C576600:ARHGEF1 protein, human; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D002352:Carrier Proteins; D064067:Rho Guanine Nucleotide Exchange Factors