Yang Qin, Zhu Min, Wang Zi, Li Hui, Zhou Weihua, Xiao Xiaojuan, Zhang Bin, Hu Weixin, Liu Jing
State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, 110 Xiangya Road, Changsha, 410078, China.
Department of pathology, Central South University, 110 Xiangya Road, Changsha, 410078, China.
Tumour Biol. 2016 Sep;37(9):12713-12723. doi: 10.1007/s13277-016-5146-3. Epub 2016 Jul 22.
The membrane-cytoskeletal protein 4.1N has recently been proposed as a tumor suppressor in a number of cancers of epithelial origin, including non-small-cell lung cancer (NSCLC). However, the molecular mechanism associated with 4.1N tumor suppression remains has not been thoroughly characterized. In this study, 4.1N was shown to directly interact with the lipid raft marker flotillin-1 through its FERM and U2 domains in several different NSCLC cell lines using immunoprecipitation, co-immunoprecipitation and pull-down assays. Moreover, 4.1N silencing/overexpression experiments in paired 95C/95D cells that are of homologous origin but varying endogenous 4.1N expression (high expression in 95C cells, low expression in 95D cells) indicated that 4.1N is involved in the suppression of cell proliferation and migration through a flotillin-1/β-catenin/Wnt pathway. Taken together, the findings of this study help to elucidate the novel tumor suppressor role of 4.1N in NSCLC.
膜细胞骨架蛋白4.1N最近被认为是包括非小细胞肺癌（NSCLC）在内的多种上皮源性癌症的肿瘤抑制因子。然而，与4.1N肿瘤抑制相关的分子机制尚未得到充分表征。在本研究中，通过免疫沉淀、共免疫沉淀和下拉试验，在几种不同的NSCLC细胞系中表明4.1N通过其FERM和U2结构域与脂筏标记物小窝蛋白-1直接相互作用。此外，在同源但内源性4.1N表达不同（95C细胞中高表达，95D细胞中低表达）的配对95C/95D细胞中进行的4.1N沉默/过表达实验表明，4.1N通过小窝蛋白-1/β-连环蛋白/Wnt途径参与细胞增殖和迁移的抑制。综上所述，本研究结果有助于阐明4.1N在NSCLC中的新型肿瘤抑制作用。
