title: The cytoplasmic extension of the integrin β6 subunit regulates epithelial-to-mesenchymal transition.
abstract: Prognosis for oral cancer patients has not improved in over 60 years due to invasion and recurrence. To understand the invasive behavior of this tumor, we evaluated the role of the αvβ6 integrin. Invasive oral SCC cells express the αvβ6 integrin, which contains an 11-amino-acid extension on its β-subunit unique to the integrin family. We determined that this β6 cytoplasmic extension regulates the composition of the intermediate filament network and the organization of signaling structures called focal contacts. The auto-phosphorylation of FAK, which is localized to focal contacts, was also regulated by the β6-cytoplasmic tail, as were the transcription factors Notch and STAT3. Lastly, we also determined that activation of MAPK required the full-length β6 integrin. Together these results indicate that the signaling critical to epithelial-to-mesenchymal transition (EMT) is regulated by the β6 integrin cytoplasmic domain.
authors: DDS, Department of Orofacial Sciences, University of California, 513 Parnassus Ave, S612, Box 0422, San Francisco, CA 94143-0422, U.S.A. Daniel.ramos@ucsf.edu.
authors: Carlin
authors: C
authors: Lee
authors: Casey
authors: C
authors: Lee
authors: Stacey
authors: S
authors: Lee
authors: Amanda
authors: A
authors: Siu
authors: Daniel M
authors: DM
authors: Ramos
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007382:Intermediate Filaments / Q000378:metabolism / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000951:Antigens, Neoplasm; D016023:Integrins; D051880:Receptors, Notch; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C073878:integrin alphavbeta6; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020928:Mitogen-Activated Protein Kinases
keywords: EMT; Notch; STAT3; integrin β6; αvβ6