Department of Gastrointestinal Surgery, The First People's Hospital of Wenling, Wenling, 317500, China.
Department of Surgery, The First People's Hospital of Wenling, Wenling, 317500, China.
Biochem Biophys Res Commun. 2019 Oct 29;519(1):113-120. doi: 10.1016/j.bbrc.2019.08.141. Epub 2019 Aug 29.
Gastric cancer (GC) is still a major lethal gastrointestinal tumor. In this study, we clarified that RAB13, which is a member of Rab GTPase family and responsible for cargos delivery between the Golgi and the plasma membrane, plays critical roles in the proliferation and the chemotherapeutic resistance in GC cells. Analyzing RAB13 expression in GC specimens, we found that its mRNA level was higher in cancerous tissues compared with normal counterparts and this increase was further associated with malignant progression of GC. Moreover, increased RAB13 indicated poor overall survival (OS) and progression free survival (PFS) in GC patients. We then found that deletion of RAB13 inhibited the proliferation and promoted the apoptosis in AGS and NCI-N87 cells, the impairments of viability which was due to reduced amount of RAB13 anchoring the plasma membrane and attenuated cellular response to EGF treatment and the activation of downstream Akt/ERK/mTOR signaling pathways accordingly. Moreover, in vitro experiments showed that RAB13 deletion enhanced the sensitization of AGS and NCI-N87 cells toward cisplatin (CDDP) and 5-fluorouracil (5-FU) treatment respectively. Together, these data demonstrate that RAB13 promotes the proliferation and confers CDDP and 5-FU resistance to GC cells, which provides experimental support to target this protein in future clinical practice.
胃癌（GC）仍然是一种主要的致命胃肠道肿瘤。在这项研究中，我们阐明了 RAB13 是 Rab GTPase 家族的成员，负责高尔基体和质膜之间的货物运输，在 GC 细胞的增殖和化疗耐药中发挥关键作用。分析 GC 标本中的 RAB13 表达，我们发现其 mRNA 水平在癌组织中高于正常组织，这种增加与 GC 的恶性进展进一步相关。此外，RAB13 增加表明 GC 患者的总生存期（OS）和无进展生存期（PFS）较差。然后我们发现，RAB13 的缺失抑制了 AGS 和 NCI-N87 细胞的增殖并促进了细胞凋亡，其活力的损害是由于 RAB13 锚定在质膜上的量减少，以及细胞对 EGF 处理的反应减弱和下游 Akt/ERK/mTOR 信号通路的激活相应减弱。此外，体外实验表明，RAB13 的缺失分别增强了 AGS 和 NCI-N87 细胞对顺铂（CDDP）和 5-氟尿嘧啶（5-FU）治疗的敏感性。综上所述，这些数据表明 RAB13 促进了 GC 细胞的增殖，并赋予了它们对 CDDP 和 5-FU 的耐药性，这为将来在临床实践中靶向该蛋白提供了实验支持。
