CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer
CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer
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CMTM3 通过促进胃癌中 Rab5 活性来降低 EGFR 表达和 EGF 介导的致瘤性
DOI：
10.1016/j.canlet.2016.11.015
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发表时间：
2017-02-01
期刊：
影响因子：
9.7
通讯作者：
Han, Wenling
中科院分区：
文献类型：
--
作者：
Yuan, Wanqiong;Liu, Baocai;Han, Wenling
CMTM 3（CKLF样MARVEL跨膜结构域3）是一种肿瘤抑制基因，参与多种类型的恶性肿瘤。CMTM 3基因敲低通过STAT 3/Twist 1/EMT信号通路促进胃癌转移表皮生长因子受体1（EGFR）的高表达与胃癌患者的肿瘤转移和不良预后显著相关。在本文中，我们表明，CMTM 3抑制表皮生长因子（EGF）介导的迁移和STAT 3信号，下调EGFR表达，通过加速EGFR降解胃癌细胞。CMTM 3与早期内体标记Rab 5和EEA 1共定位。免疫共沉淀（Co-IP）测定进一步证实CMTM 3与Rab 5相互作用。更重要的是，CMTM 3显著增加Rab 5活性。CMTM 3对EGFR表达和EGF介导的迁移的抑制作用可以被针对Rab 5的siRNA消除。最后，我们发现CMTM 3的C端区域在CMTM 3的肿瘤抑制作用中起着更重要的作用。总之，本研究表明，CMTM 3通过增强Rab 5活性降低EGFR表达，促进EGFR降解，并抑制EGF介导的胃癌细胞致瘤性。(C)2016爱思唯尔爱尔兰有限公司版权所有。
CMTM3 (CKLF-like MARVEL transmembrane domain containing 3), a tumor suppressor gene, is involved in multiple types of malignancies. CMTM3 knockdown promotes metastasis of gastric cancer via the STAT3/Twist1/EMT signaling pathway. Strong epidermal growth factor receptor1 (EGFR) expression is significantly associated with tumor metastasis and poor outcomes of gastric cancer patients. In this paper, we show that CMTM3 suppresses epidermal growth factor (EGF)-mediated migration and STAT3 signaling, downregulates EGFR expression via accelerating EGFR degradation in gastric cancer cells. CMTM3 colocalizes with early endosome markers Rab5 and EEA1. Co-immunoprecipitation (Co-IP) assay further confirms that CMTM3 interacts with Rab5. More importantly, CMTM3 markedly increases Rab5 activity. The suppressive effects of CMTM3 on EGFR expression and EGF-mediated migration can be abrogated by the siRNA against Rab5. Finally, we found that the C-terminal region of CMTM3 plays more important roles in the tumor suppressive effects of CMTM3. Overall, this study demonstrates that CMTM3 decreases EGFR expression, facilitates EGFR degradation, and inhibits the EGF-mediated tumorigenicity of gastric cancer cells via enhancing Rab5 activity. (C) 2016 Elsevier Ireland Ltd. All rights reserved.