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

Yu Wang, Jisheng Li, Yan Cui, Ting Li, Man Ng Ka, Hua Geng, Henan Li, Xing Sheng Shu, Hongyu Li, Wei Liu, Bing Luo, Qian Zhang, Tony Shu Kam Mok, Wei Zheng, Xiaoyan Qiu, Gopesh Srivastava, Jun Yu, Joseph J.Y. Sung, Anthony T.C. Chan, Dalong MaQian Tao*, Wenling Han

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5194-5201
Number of pages8
JournalCancer Research
Volume69
Issue number12
DOIs
StatePublished - Jun 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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