Rab34 regulates adhesion, migration, and invasion of breast cancer cells
- 药学院－已发表论文 
【Abstract】The small GTPase Rab34 regulates spatial distribution of the lysosomes, secretion and macropinocytosis. In this study, we found that Rab34 is over expressed in aggressive breast cancer cells, implying a potential role of Rab34 in breast cancer. Silencing Rab34 by shRNA inhibits cell migration, invasion and adhesion of breast cancer cells. Rab34 specifically binds to the cytoplasmic tail of integrin β3, and depletion of Rab34 promotes the degradation of integrin β3. Interestingly, EGF induces the translocation of Rab34 to the membrane ruffle, which is greatly enhanced by the expression of Src kinase. Accordingly, Rab34 is tyrosine phosphorylated by Src at Y247 residue. A mutant mimicking phosphorylated form of Rab34 (Rab34Y247D) promotes cell migration and invasion. Importantly, the tyrosine phosphorylation of Rab34 is inhibited in cells in suspension, and increased with the cells re-adhesion. In addition, Rab34Y247D promotes cell adhesion, and enhances integrin β3 endocytosis and recycling. The results uncover a role of Rab34 in migration and invasion of breast cancer cells and its involvement in cancer metastasis, and provide a novel mechanism of tyrosine phosphorylation of Rab34 in regulating cell migration, invasion and adhesion through modulating the endocytosis, stability and recycling of integrin β3.
Description2018年4月6日，Nature旗下的肿瘤学领域著名国际期刊Oncogene在线发表了我院王团老教授课题组的研究性论文“Rab34 regulates adhesion, migration, and invasion of breast cancer cells”。该成果首次揭示了小分子GTP酶Rab34参与调控乳腺癌的相关功能和机制。王团老教授课题组的研究发现，小分子GTP酶Rab34高表达于侵袭性乳腺癌细胞中，当用shRNA靶向敲低内源Rab34的表达，能够显著抑制高侵袭性乳腺癌细胞的迁移和侵袭能力。该论文详细探究了Rab34 对乳腺癌细胞迁移、侵袭能力的影响和相关机制， 为进一步探讨Rab34作为乳腺癌治疗靶点或早期诊断标记物提供了重要的指导意义。 研究结果发表于Oncogene（JCR一区，IF 7.5），该论文的第一作者为我院孙礼祥博士和许晓慧博士，通讯作者为洪万进教授和王团老教授。This work was supported by National Natural Science Foundation of China (No.31371353 and No.31671478) and International Science & Technology Cooperation Program of China (No.2013DFG32730). The cDNA of integrin β1 and integrin β3 were kindly provided by Dr. Jiahuai Han (State Key Laboratory of Cellular Stress Biology, Xiamen University, China).