title: Focal adhesion kinase protein regulates Wnt3a gene expression to control cell fate specification in the developing neural plate.
abstract: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linked to aggressive metastatic and invasive tumors. However, little is known about its normal embryonic function. FAK protein knockdown during early Xenopus laevis development anteriorizes the embryo. Morphant embryos express increased levels of anterior neural markers, with reciprocally reduced posterior neural marker expression. Posterior neural plate folding and convergence-extension is also inhibited. This anteriorized phenotype resembles that of embryos knocked down zygotically for canonical Wnt signaling. FAK and Wnt3a genes are both expressed in the neural plate, and Wnt3a expression is FAK dependent. Ectopic Wnt expression rescues this FAK morphant anteriorized phenotype. Wnt3a thus acts downstream of FAK to balance anterior-posterior cell fate specification in the developing neural plate. Wnt3a gene expression is also FAK dependent in human breast cancer cells, suggesting that this FAK-Wnt linkage is highly conserved. This unique observation connects the FAK- and Wnt-signaling pathways, both of which act to promote cancer when aberrantly activated in mammalian cells.
authors.affiliation: Department of Biochemistry, Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fonar
authors.forename: Yoni E
authors.initials: YE
authors.lastname: Gutkovich
authors.forename: Heather
authors.initials: H
authors.lastname: Root
authors.forename: Anastasia
authors.initials: A
authors.lastname: Malyarova
authors.forename: Emil
authors.initials: E
authors.lastname: Aamar
authors.forename: Vita M
authors.initials: VM
authors.lastname: Golubovskaya
authors.forename: Sarah
authors.initials: S
authors.lastname: Elias
authors.forename: Yaniv M
authors.initials: YM
authors.lastname: Elkouby
authors.forename: Dale
authors.initials: D
authors.lastname: Frank
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D022001:Focal Adhesions / Q000235:genetics* / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D054258:Neural Plate / Q000254:growth & development* / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D060508:Wnt3 Protein / Q000096:biosynthesis* / Q000235:genetics*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D060508:Wnt3 Protein; D029867:Xenopus Proteins; C489563:foxd1 protein, Xenopus; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases