title: Snail1 controls epithelial-mesenchymal lineage commitment in focal adhesion kinase-null embryonic cells.
abstract: Mouse embryonic cells isolated from focal adhesion kinase (FAK)-null animals at embryonic day 7.5 display multiple defects in focal adhesion remodeling, microtubule dynamics, mechanotransduction, proliferation, directional motility, and invasion. To date, the ability of FAK to modulate cell function has been ascribed largely to its control of posttranscriptional signaling cascades in this embryonic cell population. In this paper, we demonstrate that FAK unexpectedly exerts control over an epithelial-mesenchymal transition (EMT) program that commits embryonic FAK-null cells to an epithelial status highlighted by the expression of E-cadherin, desmoplakin, and cytokeratins. FAK rescue reestablished the mesenchymal characteristics of FAK-null embryonic cells to generate committed mouse embryonic fibroblasts via an extracellular signal-related kinase- and Akt-dependent signaling cascade that triggered Snail1 gene expression and Snail1 protein stabilization. These findings indentify FAK as a novel regulator of Snail1-dependent EMT in embryonic cells and suggest that multiple defects in FAK(-/-) cell behavior can be attributed to an inappropriate commitment of these cells to an epithelial, rather than fibroblastic, phenotype.
authors: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors: Xiao-Yan
authors: XY
authors: Li
authors: Xiaoming
authors: X
authors: Zhou
authors: R Grant
authors: RG
authors: Rowe
authors: Yuexian
authors: Y
authors: Hu
authors: David D
authors: DD
authors: Schlaepfer
authors: Dusko
authors: D
authors: Ilić
authors: Gregory
authors: G
authors: Dressler
authors: Ann
authors: A
authors: Park
authors: Jun-Lin
authors: JL
authors: Guan
authors: Stephen J
authors: SJ
authors: Weiss
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian / Q000166:cytology*; D047108:Embryonic Development; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051416:Focal Adhesion Protein-Tyrosine Kinases