title: CMTM3 inhibits cell growth and migration and predicts favorable survival in oral squamous cell carcinoma.
abstract: Downregulation of CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) has been reported in a number of human tumors. However, the role of CMTM3 in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we showed that the expression of CMTM3 was significantly reduced in OSCC cell lines and primary tumor specimens (P < 0.001). Methylation-specific PCR showed hypermethylation in CMTM3 promoter in a significant proportion of tumor tissues (61 %). The expression of CMTM3 was associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, and recurrence of OSCC patients (P < 0.05, n = 201). More importantly, CMTM3 expression was associated with the prognosis of OSCC patients (P < 0.001) and was an independent prognostic factor (hazard ratio = 0.593, 95 % confidence interval, 0.272-1.292; P = 0.039). Overexpression of CMTM3 inhibited the growth and migration of OSCC cells. In vivo experiments also showed that the growth of OSCC xenografts in nude mice was significantly inhibited by CMTM3 overexpression. These findings indicate that downregulation of CMTM3 due to promoter hypermethylation contributed to the proliferation and migration of OSCC cells and suggest that CMTM3 is an independent prognostic factor for the evaluation of the survival of OSCC patients.
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Heyu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing, 100081, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Center for Human Disease Genomics, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Nan
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Xuefen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing, 100081, China.
authors.forename: Jiafei
authors.initials: J
authors.lastname: Qu
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing, 100081, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing, 100081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, Beijing, 100081, China. litiejun22@vip.sina.com.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002465:Cell Movement; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology*; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; C515016:CMTM3 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D012333:RNA, Messenger
keywords: CMTM3; Oral squamous cell carcinoma; Promoter methylation; Tumor suppressor gene