TY - JOUR
T1 - 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
AU - Wang, Yu
AU - Li, Jisheng
AU - Cui, Yan
AU - Li, Ting
AU - Ka, Man Ng
AU - Geng, Hua
AU - Li, Henan
AU - Shu, Xing Sheng
AU - Li, Hongyu
AU - Liu, Wei
AU - Luo, Bing
AU - Zhang, Qian
AU - Mok, Tony Shu Kam
AU - Zheng, Wei
AU - Qiu, Xiaoyan
AU - Srivastava, Gopesh
AU - Yu, Jun
AU - Sung, Joseph J.Y.
AU - Chan, Anthony T.C.
AU - Ma, Dalong
AU - Tao, Qian
AU - Han, Wenling
PY - 2009/6/15
Y1 - 2009/6/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-08-3694
DO - 10.1158/0008-5472.CAN-08-3694
M3 - Article
C2 - 19509237
AN - SCOPUS:67449127092
SN - 0008-5472
VL - 69
SP - 5194
EP - 5201
JO - Cancer Research
JF - Cancer Research
IS - 12
ER -
