title: CMTM3 decreases EGFR expression and EGF-mediated tumorigenicity by promoting Rab5 activity in gastric cancer.
abstract: 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.
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Wanqiong
authors.initials: W
authors.lastname: Yuan
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Baocai
authors.initials: B
authors.lastname: Liu
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Mo
authors.affiliation: School of Medical and Nursing, Suzhou Health College, Suzhou, 215009, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, China. Electronic address: dingshigang222@163.com.
authors.forename: Shigang
authors.initials: S
authors.lastname: Ding
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. Electronic address: hanwl@bjmu.edu.cn.
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C515016:CMTM3 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; C427755:RAB5C protein, human; D020696:rab5 GTP-Binding Proteins
keywords: CMTM3; EGFR; Gastric cancer; Migration; Rab5