FLOT1 通过 BCAR1/ERK 信号传导促进胃癌进展和转移。
FLOT1 promotes gastric cancer progression and metastasis through BCAR1/ERK signaling.
发表日期:2023
作者:
Ran Wang, Wei Huang, Kaimei Cai, Shihan Xiao, Wuming Zhang, Xianqin Hu, Jianping Guo, Linfeng Mao, Weijie Yuan, Yi Xu, Zihua Chen, Zhikang Chen, Chen Lai
来源:
International Journal of Biological Sciences
摘要:
Flotillin-1 (FLOT1) 是 Flotillin 家族的一员,是参与信号转导和囊泡运输过程的脂筏的标志。在这里,我们发现 FLOT1 通过 ERK 信号传导与 BCAR1 相互作用,促进胃癌细胞的进展和转移。 FLOT1 调节 BCAR1 磷酸化和易位。 FLOT1 的过度表达增加,而 FLOT1 的敲低则降低胃癌细胞的增殖、迁移和侵袭。 BCAR1敲低可以阻断FLOT1诱导的胃癌细胞增殖、迁移和侵袭。野生型而非突变型BCAR1(Y410F)的重新表达可以部分恢复FLOT1敲低诱导的胃癌细胞迁移和侵袭,而这种恢复可以被ERK抑制剂抑制。此外,FLOT1和BCAR1的表达与胃癌患者的不良预后密切相关。因此,我们的研究结果证实BCAR1通过ERK信号介导FLOT1诱导的胃癌进展和转移,这可能为胃癌的治疗提供新的途径。©作者。
Flotillin-1 (FLOT1) is a member of the flotillin family and serves as a hallmark of lipid rafts involved in the process of signaling transduction and vesicular trafficking. Here, we find FLOT1 promotes gastric cancer cell progression and metastasis by interacting with BCAR1, through ERK signaling. FLOT1 regulates BCAR1 phosphorylation and translocation. Overexpression of FLOT1 increases, while knockdown of FLOT1 decreases gastric cancer cell proliferation, migration and invasion. BCAR1 knockdown could block FLOT1 induced gastric cancer cell proliferation, migration and invasion. Re-expression of wildtype rather than mutant BCAR1 (Y410F) could partially restore FLOT1 knockdown induced gastric cancer cell migration and invasion, while the restore could be inhibited by ERK inhibitor. Furthermore, FLOT1 and BCAR1 expression is closely related to gastric cancer patients' poor outcome. Thus, our findings confirm that BCAR1 mediates FLOT1 induced gastric cancer progression and metastasis through ERK signaling, which may provide a novel pathway for gastric cancer treatment.© The author(s).