title: PIPKIγ and talin couple phosphoinositide and adhesion signaling to control the epithelial to mesenchymal transition.
abstract: Epithelial cells acquire migratory/invasive and stemness traits upon conversion to the mesenchymal phenotype. The expression of E-cadherin is a key to this transition; yet precise understanding of the pathways involved in integrating E-cadherin loss to the gain of mesenchymal traits remains poorly understood. Here, we show that phosphoinositide-generating enzyme, PIPKIγ, expression is upregulated upon epithelial-mesenchymal transition (EMT) and together with the cytoskeletal protein talin assemble into a signaling complex upon E-cadherin loss. PIPKIγ and talin together control the adhesion and phosphoinositide signaling that regulates conversion to the mesenchymal phenotypes. PIPKIγ and talin regulate the stability of E-cadherin transcriptional repressors, snail and slug, induced by transforming growth factor-β1 or extracellular matrix protein. Loss of PIPKIγ or talin or their interaction impaired EMT and the acquisition of cell motility and stemness. This demonstrates a mechanism where a phosphoinositide-generating enzyme PIPKIγ couples with a cytoskeletal protein talin to control the acquisition of mesenchymal phenotypes.
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: N
authors.initials: N
authors.lastname: Thapa
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: X
authors.identifier: 0000-0003-3300-2240
authors.initials: X
authors.lastname: Tan
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: S
authors.initials: S
authors.lastname: Choi
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: T
authors.initials: T
authors.lastname: Wise
authors.affiliation: Molecular and Cellular Pharmacology Program, University of Wisconsin-Madison, School of Medicine and Public Health, Madison, WI, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016608:Talin / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; D010716:Phosphatidylinositols; D016608:Talin; D053773:Transforming Growth Factor beta1; C496077:Tln1 protein, mouse; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase