RAB13 as a novel prognosis marker promotes proliferation and chemotherapeutic resistance in gastric cancer
RAB13 as a novel prognosis marker promotes proliferation and chemotherapeutic resistance in gastric cancer
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DOI：
10.1016/j.bbrc.2019.08.141
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发表时间：
2019-10-29
影响因子：
3.1
通讯作者：
Mao, Chenyang
中科院分区：
文献类型：
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作者：
Chen, Peng;Chen, Guofu;Mao, Chenyang
胃癌（GC）仍然是主要的致死性胃肠道肿瘤。在本研究中，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传递，在 GC 细胞的增殖和化疗耐药中发挥着关键作用。分析GC标本中RAB13的表达，我们发现其mRNA水平在癌组织中高于正常组织，并且这种增加进一步与GC的恶性进展相关。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，这是由于锚定质膜的 RAB13 量减少、细胞对 EGF 处理的反应减弱以及下游 Akt/ERK/mTOR 信号通路的激活而导致的活力受损。此外，体外实验表明，RAB13缺失分别增强了AGS和NCIN87细胞对顺铂（CDDP）和5-氟尿嘧啶（5-FU）治疗的敏感性。总之，这些数据表明 RAB13 促进增殖并赋予 GC 细胞 CDDP 和 5-FU 抗性，这为未来临床实践中靶向该蛋白提供了实验支持。 (C) 2019 Elsevier Inc. 保留所有权利。
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 NCIN87 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. (C) 2019 Elsevier Inc. All rights reserved.