title: CMTM3 inhibits human testicular cancer cell growth through inducing cell-cycle arrest and apoptosis.
abstract: Human CMTM3 has been proposed as a putative tumor suppressor gene. The loss of CMTM3 has been found in several carcinomas. However, the regulation of CMTM3 expression and its function in tumor progression remain largely unknown. Here, we investigated the regulation of CMTM3 expression, function and molecular mechanism in human testicular cancer cells. CMTM3 was frequently downregulated or silenced in testicular cancer cell lines and tumor tissues but highly expressed in normal testis tissues. The re-expression of CMTM3 significantly suppressed the colony formation, proliferation, and migration capacity of testicular cancer cells by inducing a G2 cell cycle arrest and apoptosis. Moreover, the re-expression of CMTM3 activated the transcription of p53, induced p53 accumulation, up-regulated the expression of p21, and increased the cleavage of caspase 9, 8, 3, and PARP. The downregulation of CMTM3 in clinical tumor tissues was associated with the methylation of a single CpG site located within the Sp1/Sp3-responsive region of the core promoter. These results indicate that CMTM3 can function as tumor suppressor through the induction of a G2 cell cycle arrest and apoptosis. CMTM3 is thus involved in testicular cancer pathogenesis, and it is frequently at least partially silenced by the methylation of a single, specific CpG site in tumor tissues.
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Zesong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Guandong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China ; Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Guandong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
authors.forename: Jianting
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Urology, Suzhou municipal Hospital, Suzhou, Anhui, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Nie
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Aifa
authors.initials: A
authors.lastname: Tang
authors.affiliation: Department of Clinical Laboratory, Peking University Shenzhen Hospital, Shenzhen, China.
authors.forename: Xianxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Liu
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Mei
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Guandong Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Center, Shenzhen, China.
authors.forename: Yaoting
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Cai
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C515016:CMTM3 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins