title: Overexpression of integrin αv facilitates proliferation and invasion of oral squamous cell carcinoma cells via MEK/ERK signaling pathway that is activated by interaction of integrin αvβ8 with type Ⅰ collagen.
abstract: To examine the role of integrin αv subunit in the progression of squamous cell carcinoma (SCC), oral SCC cells were stably transfected with integrin αv cDNA. Integrin αv transfectants exhibited the enhancement of proliferation on type Ⅰ collagen, and seemed to have a high ability to invade type Ⅰ collagen gel. Overexpression of integrin αv led to rapid phosphorylation of focal adhesion kinase (FAK), mitogen‑activated protein kinase kinase 1/2 (MEK1/2) and extracellular signal‑regulated kinase 1/2 (ERK1/2) in SCC cells on type Ⅰ collagen. The downregulation of integrin β8 in integrin αv transfectants by its specific antisense oligonucleotide led to a decrease in type Ⅰ collagen‑stimulated activation of FAK and the MEK/ERK signaling pathway, and also suppressed the proliferation on type Ⅰ collagen and the invasiveness into type Ⅰ collagen gel. Moreover, the expression of integrin β8 was induced following transfection with integrin αv cDNA. These results indicated that the overexpression of integrin αv induces integrin αvβ8 heterodimer formation and the binding of integrin αvβ8 to type Ⅰ collagen might enhance the proliferation and invasion of SCC cells via the activation of the MEK/ERK signaling pathway.
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Hayashido
authors.affiliation: Department of Oral Surgery, Nihon University Itabashi Hospital, Itabashi‑ku, Tokyo 173‑8610, Japan.
authors.forename: Hisataka
authors.initials: H
authors.lastname: Kitano
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Sakaue
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Mirei
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakurai
authors.affiliation: Department of Molecular Oral Medicine and Maxillofacial Surgery, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami‑ku, Hiroshima 734‑8553, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Okamoto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000096:biosynthesis* / Q000235:genetics; D016023:Integrins / Q000096:biosynthesis* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000235:genetics; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics
chemical_list: D024042:Collagen Type I; D039564:Integrin alphaV; D016023:Integrins; C403414:integrin alphavbeta8