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

To examine the role of integrin alpha v subunit in the progression of squamous cell carcinoma (SCC), oral SCC cells were stably transfected with integrin av cDNA. Integrin alpha v 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 alpha v 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 beta 8 in integrin alpha v 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 (38 was induced following transfection with integrin av cDNA. These results indicated that the overexpression of integrin av induces integrin alpha v beta 8 heterodimer formation and the binding of integrin alpha v beta 8 to type I collagen might enhance the proliferation and invasion of SCC cells via the activation of the MEK/ERK signaling pathway.