title: Cyclin A2, a novel regulator of EMT.
abstract: Our previous work showed that Cyclin A2 deficiency promotes cell invasion in fibroblasts. Given that the majority of cancers emerge from epithelia, we explored novel functions for Cyclin A2 by depleting it in normal mammary epithelial cells. This caused an epithelial to mesenchymal transition (EMT) associated with loss of cell-to-cell contacts, decreased E-Cadherin expression and increased invasive properties characterized by a reciprocal regulation of RhoA and RhoC activities, where RhoA-decreased activity drove cell invasiveness and E-Cadherin delocalization, and RhoC-increased activity only supported cell motility. Phenotypes induced by Cyclin A2 deficiency were exacerbated upon oncogenic activated-Ras expression, which led to an increased expression of EMT-related transcriptional factors. Moreover, Cyclin A2-depleted cells exhibited stem cell-like properties and increased invasion in an in vivo avian embryo model. Our work supports a model where Cyclin A2 downregulation facilitates cancer cell EMT and metastatic dissemination.
authors.affiliation: Institut de Génétique Moléculaire de Montpellier, CNRS, 1919 route de Mende, 34293, Montpellier, France.
authors.forename: Nawal
authors.initials: N
authors.lastname: Bendris
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Cheung
authors.forename: Hon Sing
authors.initials: HS
authors.lastname: Leong
authors.forename: John D
authors.initials: JD
authors.lastname: Lewis
authors.forename: Ann F
authors.initials: AF
authors.lastname: Chambers
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Blanchard
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Lemmers
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000235:genetics; D056751:Cyclin A2 / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D015820:Cadherins; D056751:Cyclin A2; D005353:Fibronectins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; C512911:Rhoc protein, mouse; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein