Oncotarget

Research Papers:

CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation

Baocai Liu _, Yu Su, Ting Li, Wanqiong Yuan, Xiaoning Mo, Henan Li, Qihua He, Dalong Ma and Wenling Han

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:41092-41107. https://doi.org/10.18632/oncotarget.5732

Metrics: PDF 1622 views  |   HTML 1612 views  |   ?  


Abstract

Baocai Liu1,*, Yu Su1,2,*, Ting Li1, Wanqiong Yuan1, Xiaoning Mo1, Henan Li1,3, Qihua He4, Dalong Ma1, Wenling Han1

1Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China

2Department of Clinical Laboratory, Beijing Jishuitan Hospital, Beijing, China

3Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China

4Peking University Medical and Health Analysis Center, Beijing, China

*These authors have contributed equally to this work

Correspondence to:

Wenling Han, e-mail: hanwl@bjmu.edu.cn

Keywords: NSCLC, CMTM7, EGFR, AKT, Rab5

Received: May 01, 2015     Accepted: September 19, 2015     Published: October 26, 2015

ABSTRACT

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5732