整合素 αvβ8 与 I 型胶原蛋白的相互作用被证明可以通过丝裂原激活蛋白激酶/细胞外信号调节激酶途径促进口腔鳞状细胞癌 (SCC) 细胞增殖。然而，整合素αvβ8在鳞状细胞癌进展中的作用仍然知之甚少。因此，本研究探讨了整合素αvβ8在口腔鳞状细胞癌进展中的作用。通过蛋白质印迹法检测口腔鳞状细胞癌细胞中整合素αv和β8蛋白的表达。使用改良的博伊登室测定法研究口腔鳞状细胞癌细胞的运动性。使用 I 型胶原凝胶在三维培养中检查口腔鳞状细胞癌细胞的行为。通过 Pull-down 实验分析口腔 SCC 细胞的 Ras 同源家族成员 A (RHOA)、Ras 相关 C3 肉毒毒素底物 1 (RAC1) 和细胞分裂控制蛋白 42 同源 (CDC42) 活性。具有高整合素 αvβ8 的 SCC 细胞表达水平在 I 型胶原蛋白上具有很高的迁移能力，并表现出增强的对 I 型胶原蛋白凝胶的侵袭能力。在具有高整合素 αvβ8 表达水平的 SCC 细胞中，I 型胶原培养诱导 RAC1 激活。 RAC1抑制剂治疗降低了I型胶原诱导的鳞状细胞癌细胞的运动性。特异性反义寡核苷酸下调整合素β8可减少I型胶原诱导的RAC1激活，并抑制细胞运动和对I型胶原凝胶的侵袭。整合素αvβ8与I型胶原的相互作用通过RAC1激活促进SCC细胞运动和侵袭。因此，整合素αvβ8和RAC1可能代表抑制口腔SCC患者转移和侵袭的新靶点。版权所有©2023国际抗癌研究所（George J. Delinasios博士），保留所有权利。

The interaction of integrin αvβ8 with type I collagen was shown to promote oral squamous cell carcinoma (SCC) cell proliferation via the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. However, the role of integrin αvβ8 in SCC progression remains poorly understood. In this study, the role of integrin αvβ8 in oral SCC progression was therefore investigated.Integrin αv and β8 protein expression in oral SCC cells was examined by western blotting. Oral SCC cell motility was investigated using modified Boyden chamber assays. Behavior of oral SCC cells was examined in three-dimensional culture using type I collagen gel. Ras homolog family member A (RHOA), Ras-related C3 botulinum toxin substrate 1 (RAC1), and cell division control protein 42 homolog (CDC42) activity of oral SCC cells was analyzed by pull-down assays.SCC cells with high integrin αvβ8 expression levels had a high ability to migrate on type I collagen and exhibited enhanced invasion into type I collagen gel. In SCC cells with high integrin αvβ8 expression level, cultivation on type I collagen induced RAC1 activation. Treatment with RAC1 inhibitor reduced type I collagen-induced motility of SCC cells. Down-regulation of integrin β8 by specific antisense oligonucleotide reduced type I collagen-induced RAC1 activation and suppressed cell motility and invasion into type I collagen gel.The interaction of integrin αvβ8 with type I collagen facilitates SCC cell motility and invasion via RAC1 activation. Therefore, integrin αvβ8 and RAC1 may represent new targets for inhibiting metastasis and invasion in patients with oral SCC.Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.