Jian Qiang, Miao Ye, Tang Li, Huang Min, Yang Yi, Ba Wei, Liu Yali, Chi Sumin, Li Chengxin
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Department of Dermatology, Chinese People's Liberation Army General Hospital, Beijing, China.
Oncotarget. 2016 Feb 2;7(5):5342-52. doi: 10.18632/oncotarget.6701.
Rab23 was a member of Ras-related small GTPase family, which played a key role in the regulation of Shh signaling pathway. However, the function and regulatory mechanism of Rab23 in cutaneous squamous cell carcinoma was unknown. In this study, we found that the expression level of Rab23 was higher in moderately to poorly tumor differentiation tissue and non-exposed positions, and no statistically significant difference showed in Rab23 expression according to trauma/chronic disease, location on lips/ears, tumor size, gender, or age. Interestingly, we found that Rab23 RNAi suppressed cell invasion and Rab23 overexpression promoted cell invasion depended on GTP-bound form of Rab23. Inhibition of Rac1 activity or Rac1 silencing with siRNA fragment attenuated Rab23 promoted cells migration and invasion. Notably, we confirmed that Rab23 was co-localized with integrin β1 in cell membrane of Rab23 WT and Rab23 Q68L stable expression cells and Rab23 efficiently coprecipitated with integrin β1 and Tiam1 in a GTP-dependent manner. Further, integrin β1 siRNA interrupted the coprecipitation between Rab23 and Tiam1 and attenuated Rab23 promoted cells migration and invasion. Taken together, our results indicated that Rab23 promotes squamous cell carcinoma cells migration and invasion by regulating Integrin β1/Tiam1/Rac1 pathway.
Rab23是Ras相关小GTP酶家族的成员,在Shh信号通路的调节中起关键作用。然而,Rab23在皮肤鳞状细胞癌中的功能和调控机制尚不清楚。在本研究中,我们发现Rab23在中度至低度肿瘤分化组织和非暴露部位的表达水平较高,并且根据创伤/慢性疾病、唇/耳部位、肿瘤大小、性别或年龄,Rab23表达无统计学显著差异。有趣的是,我们发现Rab23 RNA干扰抑制细胞侵袭,而Rab23过表达促进细胞侵袭,这取决于Rab23的GTP结合形式。用siRNA片段抑制Rac1活性或沉默Rac1可减弱Rab23促进的细胞迁移和侵袭。值得注意的是,我们证实Rab23在Rab23野生型和Rab23 Q68L稳定表达细胞的细胞膜中与整合素β1共定位,并且Rab23以GTP依赖的方式与整合素β1和Tiam1有效共沉淀。此外,整合素β1 siRNA中断了Rab23与Tiam1之间的共沉淀,并减弱了Rab23促进的细胞迁移和侵袭。综上所述,我们的结果表明Rab23通过调节整合素β1/Tiam1/Rac1途径促进鳞状细胞癌细胞的迁移和侵袭。