title: CMTM3, located at the critical tumor suppressor locus 16q22.1, is silenced by CpG methylation in carcinomas and inhibits tumor cell growth through inducing apoptosis.
abstract: Closely located at the tumor suppressor locus 16q22.1, CKLF-like MARVEL transmembrane domain-containing member 3 and 4 (CMTM3 and CMTM4) encode two CMTM family proteins, which link chemokines and the transmembrane-4 superfamily. In contrast to the broad expression of both CMTM3 and CMTM4 in normal human adult tissues, only CMTM3 is silenced or down-regulated in common carcinoma (gastric, breast, nasopharyngeal, esophageal, and colon) cell lines and primary tumors. CMTM3 methylation was not detected in normal epithelial cell lines and tissues, with weak methylation present in only 5 of 35 (14%) gastric cancer adjacent normal tissues. Furthermore, immunohistochemistry showed that CMTM3 protein was absent in 12 of 35 (34%) gastric and 1 of 2 colorectal tumors, which was well correlated with its methylation status. The silencing of CMTM3 is due to aberrant promoter CpG methylation that could be reversed by pharmacologic demethylation. Ectopic expression of CMTM3 strongly suppressed the colony formation of carcinoma cell lines. In addition, CMTM3 inhibited tumor cell growth and induced apoptosis with caspase-3 activation. Thus, CMTM3 exerts tumor-suppressive functions in tumor cells, with frequent epigenetic inactivation by promoter CpG methylation in common carcinomas.
authors.affiliation: Peking University Center for Human Disease Genomics, Department of Immunology, Health Science Center, Peking University, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Jisheng
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Ka Man
authors.initials: KM
authors.lastname: Ng
authors.forename: Hua
authors.initials: H
authors.lastname: Geng
authors.forename: Henan
authors.initials: H
authors.lastname: Li
authors.forename: Xing-sheng
authors.initials: XS
authors.lastname: Shu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Tony Shu Kam
authors.initials: TS
authors.lastname: Mok
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qiu
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Anthony T C
authors.initials: AT
authors.lastname: Chan
authors.forename: Dalong
authors.initials: D
authors.lastname: Ma
authors.forename: Qian
authors.initials: Q
authors.lastname: Tao
authors.forename: Wenling
authors.initials: W
authors.lastname: Han
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C515016:CMTM3 protein, human; D018925:Chemokines; D017931:DNA Primers; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins