title: CRB3A Controls the Morphology and Cohesion of Cancer Cells through Ehm2/p114RhoGEF-Dependent Signaling.
abstract: The transmembrane protein CRB3A controls epithelial cell polarization. Elucidating the molecular mechanisms of CRB3A function is essential as this protein prevents the epithelial-to-mesenchymal transition (EMT), which contributes to tumor progression. To investigate the functional impact of altered CRB3A expression in cancer cells, we expressed CRB3A in HeLa cells, which are devoid of endogenous CRB3A. While control HeLa cells display a patchy F-actin distribution, CRB3A-expressing cells form a circumferential actomyosin belt. This reorganization of the cytoskeleton is accompanied by a transition from an ameboid cell shape to an epithelial-cell-like morphology. In addition, CRB3A increases the cohesion of HeLa cells. To perform these functions, CRB3A recruits p114RhoGEF and its activator Ehm2 to the cell periphery using both functional motifs of its cytoplasmic tail and increases RhoA activation levels. ROCK1 and ROCK2 (ROCK1/2), which are critical effectors of RhoA, are also essential to modulate the cytoskeleton and cell shape downstream of CRB3A. Overall, our study highlights novel roles for CRB3A and deciphers the signaling pathway conferring to CRB3A the ability to fulfill these functions. Thereby, our data will facilitate further investigation of CRB3A functions and increase our understanding of the cellular defects associated with the loss of CRB3A expression in cancer cells.
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU de Québec, Oncology Axis, Québec, Canada.
authors.forename: Elise
authors.initials: E
authors.lastname: Loie
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU de Québec, Oncology Axis, Québec, Canada.
authors.forename: Lucie E
authors.initials: LE
authors.lastname: Charrier
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU de Québec, Oncology Axis, Québec, Canada.
authors.forename: Kévin
authors.initials: K
authors.lastname: Sollier
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU de Québec, Oncology Axis, Québec, Canada.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Masson
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology/Cancer Research Center, Laval University, and CRCHU de Québec, Oncology Axis, Québec, Canada Patrick.Laprise@crchudequebec.ulaval.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Laprise
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D002448:Cell Adhesion; D048430:Cell Shape; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004285:Dogs; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D024462:Myosin Type II / Q000378:metabolism; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C577230:ARHGEF18 protein, human; C472002:CRB3 protein, human; D003598:Cytoskeletal Proteins; C478965:EPB41L4B protein, human; D008562:Membrane Glycoproteins; D064067:Rho Guanine Nucleotide Exchange Factors; D024462:Myosin Type II