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.
Department of Oral Surgery, Nihon University Itabashi Hospital, Itabashi‑ku, Tokyo 173‑8610, Japan.
Int J Oncol. 2014 Nov;45(5):1875-82. doi: 10.3892/ijo.2014.2642. Epub 2014 Sep 4.
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.
为了研究整合素 αv 亚基在鳞状细胞癌（SCC）进展中的作用，我们将整合素 αv cDNA 稳定转染入口腔 SCC 细胞。整合素 αv 转染细胞在Ⅰ型胶原上表现出增殖能力增强的特征，并且似乎具有高侵袭Ⅰ型胶原凝胶的能力。在Ⅰ型胶原上，整合素 αv 的过表达导致 SCC 细胞中粘着斑激酶（FAK）、丝裂原活化蛋白激酶激酶 1/2（MEK1/2）和细胞外信号调节激酶 1/2（ERK1/2）的快速磷酸化。整合素 αv 转染细胞中整合素 β8 的特异性反义寡核苷酸下调导致Ⅰ型胶原刺激的 FAK 和 MEK/ERK 信号通路的激活减少，并抑制了在Ⅰ型胶原上的增殖和侵袭进入Ⅰ型胶原凝胶。此外，整合素 αv cDNA 的转染诱导了整合素 β8 的表达。这些结果表明，整合素 αv 的过表达诱导整合素 αvβ8 异二聚体的形成，并且整合素 αvβ8 与Ⅰ型胶原的结合可能通过激活 MEK/ERK 信号通路增强 SCC 细胞的增殖和侵袭。
