State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, China.
Department of Obstetrics and Gynecology, Fengxian Hospital, Shanghai 201499, China.
J Immunol Res. 2018 May 24;2018:4602570. doi: 10.1155/2018/4602570. eCollection 2018.
Integrin subunit alpha 9 (ITGA9) mediates cell-cell and cell-matrix adhesion, cell migration, and invasion through binding different kinds of extracellular matrix (ECM) components. However, its potential role and underlying molecular mechanisms remain unclear in hepatocellular carcinoma (HCC). Here, we found that ITGA9 expression was obviously decreased in patients with HCC, which was negatively correlated with HCC growth and metastasis. ITGA9 overexpression significantly inhibited cell proliferation and migration as well as tumor growth and metastasis . Our data demonstrated that the inhibitory effect of ITGA9 on HCC cell motility was associated with reduced phosphorylation of focal adhesion kinase (FAK) and c-Src tyrosine kinase (Src), disrupted focal adhesion reorganization, and decreased Rac1 and RhoA activity. Our data suggest ITGA9, as a suppressor of HCC, prevents tumor cell migration and invasiveness through FAK/Src-Rac1/RhoA signaling.
整合素亚基 alpha9（ITGA9）通过与不同种类的细胞外基质（ECM）成分结合，介导细胞-细胞和细胞-基质黏附、细胞迁移和侵袭。然而，其在肝细胞癌（HCC）中的潜在作用和潜在分子机制仍不清楚。在这里，我们发现 HCC 患者中 ITGA9 的表达明显降低，与 HCC 的生长和转移呈负相关。ITGA9 的过表达显著抑制了细胞增殖和迁移以及肿瘤的生长和转移。我们的数据表明，ITGA9 对 HCC 细胞迁移的抑制作用与粘着斑激酶（FAK）和 c-Src 酪氨酸激酶（Src）的磷酸化减少、粘着斑重排破坏以及 Rac1 和 RhoA 活性降低有关。我们的数据表明，ITGA9 作为 HCC 的抑制剂，通过 FAK/Src-Rac1/RhoA 信号通路防止肿瘤细胞的迁移和侵袭。
