title: Mechanisms that link the oncogenic epithelial-mesenchymal transition to suppression of anoikis.
abstract: The oncogenic epithelial-mesenchymal transition (EMT) contributes to tumor progression in various context-dependent ways, including increased metastatic potential, expansion of cancer stem cell subpopulations, chemo-resistance and disease recurrence. One of the hallmarks of EMT is resistance of tumor cells to anoikis. This resistance contributes to metastasis and is a defining property not only of EMT but also of cancer stem cells. Here, we review the mechanistic coupling between EMT and resistance to anoikis. The discussion focuses on several key aspects. First, we provide an update on new pathways that lead from the loss of E-cadherin to anoikis resistance. We then discuss the relevance of transcription factors that are crucial in wound healing in the context of oncogenic EMT. Next, we explore the consequences of the breakdown of cell-polarity complexes upon anoikis sensitivity, through the Hippo, Wnt and transforming growth factor β (TGF-β) pathways, emphasizing points of crossregulation. Finally, we summarize the direct regulation of cell survival genes through EMT-inducing transcription factors, and the roles of the tyrosine kinases focal adhesion kinase (FAK) and TrkB neurotrophin receptor in EMT-related regulation of anoikis. Emerging from these studies are unifying principles that will lead to improvements in cancer therapy by reprogramming sensitivity of anoikis.
authors.affiliation: Department of Biochemistry, West Virginia University, Morgantown, WV 26506, USA. sfrisch@hsc.wvu.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Frisch
authors.forename: Michael
authors.initials: M
authors.lastname: Schaller
authors.forename: Benjamin
authors.initials: B
authors.lastname: Cieply
mesh_terms: D000818:Animals; D023102:Anoikis / Q000235:genetics / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta; D051416:Focal Adhesion Protein-Tyrosine Kinases