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.
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.
Wang
Yu
Y
Peking University Center for Human Disease Genomics, Department of Immunology, Health Science Center, Peking University, Beijing, China.
Li
Jisheng
J
Cui
Yan
Y
Li
Ting
T
Ng
Ka Man
KM
Geng
Hua
H
Li
Henan
H
Shu
Xing-sheng
XS
Li
Hongyu
H
Liu
Wei
W
Luo
Bing
B
Zhang
Qian
Q
Mok
Tony Shu Kam
TS
Zheng
Wei
W
Qiu
Xiaoyan
X
Srivastava
Gopesh
G
Yu
Jun
J
Sung
Joseph J Y
JJ
Chan
Anthony T C
AT
Ma
Dalong
D
Tao
Qian
Q
Han
Wenling
W
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
C515016:CMTM3 protein, human; D018925:Chemokines; D017931:DNA Primers; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins