Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China; Liver Cancer Center, No. 5 Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Life Sci. 2019 Apr 1;222:168-174. doi: 10.1016/j.lfs.2019.03.003. Epub 2019 Mar 7.
SDF-1α induced chemotaxis plays an important role in hepatocellular carcinoma metastasis. CXCR4 stimulated by SDF-1α/CXCL12 triggers heterotrimeric G proteins activation, which regulate migration and chemotaxis of hepatocellular carcinoma cells. The pathways linking the chemokine GPCR/Gi signaling to actin polymerization for migration of cancer cells are not known.
Through would healing assay, chemotaxis assay, F-actin polymerization assay, confocal assay, immunohistochemical assay, protein identification and coimmunoprecipitation assay, we detected the role and mechanisms of Annexin A2 in hepatocellular carcinoma.
In the present study, we firstly investigated the role of Annexin A2 in HepG2 cell chemotaxis and metastasis. Immunohistochemical analysis showed that Annexin A2 was highly expressed in hepatocellular carcinoma tissues. Its expression was closely associated with lymph node and distant metastasis. Knockdown Annexin A2 impaired cancer cell chemotaxis. Co-immunoprecipitation results showed an interaction between Annexin A2 and ELMO1. CXCL12 triggers an ELMO1-dependent membrane translocation of Annexin A2.
Taken together, our results indicated an important role of Annexin A2 in hepatocellular carcinoma tissues metastasis and revealed a novel molecular mechanism of its activation.
SDF-1α诱导的趋化作用在肝细胞癌转移中起着重要作用。SDF-1α/CXCL12 刺激的 CXCR4 触发异三聚体 G 蛋白的激活，调节肝癌细胞的迁移和趋化性。趋化因子 GPCR/Gi 信号与肌动蛋白聚合以促进癌细胞迁移的途径尚不清楚。
通过伤口愈合试验、趋化性试验、F-肌动蛋白聚合试验、共聚焦试验、免疫组织化学试验、蛋白质鉴定和免疫共沉淀试验，检测 Annexin A2 在肝癌中的作用和机制。
在本研究中，我们首次研究了 Annexin A2 在 HepG2 细胞趋化性和转移中的作用。免疫组织化学分析显示 Annexin A2 在肝癌组织中高表达。其表达与淋巴结和远处转移密切相关。敲低 Annexin A2 会损害癌细胞的趋化性。免疫共沉淀结果显示 Annexin A2 与 ELMO1 之间存在相互作用。CXCL12 触发 Annexin A2 依赖于 ELMO1 的膜易位。
综上所述，我们的研究结果表明 Annexin A2 在肝癌组织转移中起重要作用，并揭示了其激活的新分子机制。
