title: Par6 is phosphorylated by aPKC to facilitate EMT.
abstract: The conserved polarity proteins Par6 and aPKC regulate cell polarization processes. However, increasing evidence also suggests that they play a role in oncogenic progression. During tumor progression, epithelial to mesenchymal transition (EMT) delineates an evolutionary conserved process that converts stationary epithelial cells into mesenchymal cells, which have an acquired ability for independent migration and invasion. In addition to signaling pathways that alter genetic programes that trigger the loss of cell-cell adhesion, alternative pathways can alter cell plasticity to regulate cell-cell cohesion and increase invasive potential. One such pathway involves TGFβ-induced phosphorylation of Par6. In epithelial cells, Par6 phosphorylation results in the dissolution of junctional complexes, cytoskeletal remodelling, and increased metastatic potential. Recently, we found that aPKC can also phosphorylate Par6 to drive EMT and increase the migratory potential of non-small cell lung cancer cells. This result has implications with respect to homeostatic and developmental processes involving polarization, and also with respect to cancer progression-particularly since aPKC has been reported to be an oncogenic regulator in various tumor cells.
authors.affiliation: Department of Physiology and Pharmacology; Western University; London, ON, Canada.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gunaratne
authors.forename: Gianni M
authors.initials: GM
authors.lastname: Di Guglielmo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016212:Transforming Growth Factor beta; D011493:Protein Kinase C
keywords: EMT; Par3; Par6; RhoA; Smurf1; TGFÎ²; aPKC; cell polarity