Liver Cancer Institute, Shanghai Medical School, Fudan University, Zhongshan Hospital, Shanghai, People's Republic of China.
PLoS One. 2011;6(9):e24901. doi: 10.1371/journal.pone.0024901. Epub 2011 Sep 22.
Tetraspanin CD151 has been implicated in metastasis through forming complexes with different molecular partners. In this study, we mapped tetraspanin web proteins centered on CD151, in order to explore the role of CD151 complexes in the progression of hepatocellular carcinoma (HCC). Immunoprecipitation was used to isolate tetraspanin complexes from HCCLM3 cells using a CD151 antibody, and associated proteins were identified by mass spectrometry. The interaction of CD151 and its molecular partners, and their roles in invasiveness and metastasis of HCC cells were assayed through disruption of the CD151 network. Finally, the clinical implication of CD151 complexes in HCC patients was also examined. In this study, we identified 58 proteins, characterized the tetraspanin CD151 web, and chose integrin β1 as a main partner to further investigate. When the CD151/integrin β1 complex in HCC cells was disrupted, migration, invasiveness, secretion of matrix metalloproteinase 9, and metastasis were markedly influenced. However, both CD151 and integrin β1 expression were untouched. HCC patients with high expression of CD151/integrin β1 complex had the poorest prognosis of the whole cohort of patients. Together, our data show that CD151 acts as an important player in the progression of HCC in an integrin β1-dependent manner.
四跨膜蛋白 CD151 已被牵连到转移过程中，通过与不同的分子伴侣形成复合物。在这项研究中，我们以 CD151 为中心，绘制了四跨膜蛋白网络蛋白，以探讨 CD151 复合物在肝细胞癌 (HCC) 进展中的作用。我们使用 CD151 抗体通过免疫沉淀从 HCCLM3 细胞中分离四跨膜蛋白复合物，并通过质谱鉴定相关蛋白。通过破坏 CD151 网络来检测 CD151 与其分子伴侣的相互作用及其在 HCC 细胞侵袭和转移中的作用。最后，还检查了 CD151 复合物在 HCC 患者中的临床意义。在这项研究中，我们鉴定了 58 种蛋白质，描绘了四跨膜蛋白 CD151 网络，并选择整合素 β1 作为主要伴侣进一步研究。当 HCC 细胞中的 CD151/整合素 β1 复合物被破坏时，迁移、侵袭、基质金属蛋白酶 9 的分泌和转移明显受到影响。然而，CD151 和整合素 β1 的表达都没有受到影响。CD151/整合素 β1 复合物高表达的 HCC 患者的预后是整个患者队列中最差的。总之，我们的数据表明，CD151 以整合素 β1 依赖的方式在 HCC 的进展中起着重要作用。
