CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.
CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.
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CMTM7 敲低通过减少 Rab5 激活来增加人类非小细胞肺癌细胞的致瘤性和 EGFR-AKT 信号传导。
DOI：
10.18632/oncotarget.5732
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Han W
中科院分区：
文献类型：
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作者：
Liu B;Su Y;Li T;Yuan W;Mo X;Li H;He Q;Ma D;Han W
表皮生长因子受体（EGFR）信号转导的失调已被充分证明有助于非小细胞肺癌（NSCLC）的进展，非小细胞肺癌是世界上癌症死亡的主要原因。EGF刺激的EGFR活化诱导受体内化和降解，其在EGFR信号传导中起重要作用。这一过程在癌细胞中经常失调，导致EGFR水平和信号传导增强。我们以前对CMTM 7的研究仅限于简单描述过表达的CMTM 7与EGFR-AKT信号传导的关系。内源性CMTM 7的生物学功能及其分子机制尚不清楚。在这项研究中，我们表明CMTM 7的稳定敲除增强了NSCLC细胞的恶性潜能，并通过减少EGFR内化和降解增强了EGFR-AKT信号传导。从机制上讲，CMTM 7敲低降低了Rab 5的激活，Rab 5是一种已知早期内体融合所需的蛋白质。因此，在NSCLC中，CMTM 7的缺失将有助于维持异常EGFR介导的致癌信号传导。总之，我们的研究结果突出了CMTM 7在肿瘤细胞中EGFR信号传导调节中的作用，揭示了CMTM 7作为与Rab 5激活相关的新型分子。
The dysregulation of epidermal growth factor receptor (EGFR) signaling has been well documented to contribute to the progression of non-small cell lung cancer (NSCLC), the leading cause of cancer death in the world. EGF-stimulated EGFR activation induces receptor internalization and degradation, which plays an important role in EGFR signaling. This process is frequently deregulated in cancer cells, leading to enhanced EGFR levels and signaling. Our previous study on CMTM7 is only limited to a brief description of the relationship of overexpressed CMTM7 with EGFR-AKT signaling. The biological functions of endogenous CMTM7 and its molecular mechanism remained unclear. In this study, we show that the stable knockdown of CMTM7 augments the malignant potential of NSCLC cells and enhances EGFR-AKT signaling by decreasing EGFR internalization and degradation. Mechanistically, CMTM7 knockdown reduces the activation of Rab5, a protein known to be required for early endosome fusion. In NSCLC, the loss of CMTM7 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Together, our findings highlight the role of CMTM7 in the regulation of EGFR signaling in tumor cells, revealing CMTM7 as a novel molecule related to Rab5 activation.