title: CMTM7 knockdown increases tumorigenicity of human non-small cell lung cancer cells and EGFR-AKT signaling by reducing Rab5 activation.
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.
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Liu
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.|Department of Clinical Laboratory, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Su
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Wanqiong
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mo
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.|Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
authors.forename: Henan
authors.initials: H
authors.lastname: Li
authors.affiliation: Peking University Medical and Health Analysis Center, Beijing, China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics / Q000378:metabolism*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018613:Microscopy, Confocal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism*
chemical_list: C552173:CMTM7 protein, human; D018925:Chemokines; D008164:Luminescent Proteins; D062792:MARVEL Domain-Containing Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C427755:RAB5C protein, human; D020696:rab5 GTP-Binding Proteins
keywords: AKT; CMTM7; EGFR; NSCLC; Rab5