title: Epigenetic silencing of TPM2 contributes to colorectal cancer progression upon RhoA activation.
abstract: Beta-tropomyosin (β-tropomyosin, TPM2) has been found to be downregulated in colorectal cancer (CRC) in previous studies. In this study, we aimed to investigate the mechanisms and potential biological consequences of the downregulation of TPM2 in colorectal cancer. TPM2 expression in colorectal cancer was assessed by qRT-PCR and immunostaining. The biological functions of TPM2 were assessed in cell lines either overexpressing or underexpressingTPM2. Aberrant DNA methylation in the promoter region is associated with suppression of TPM2 expression in primary colorectal cancer tissue samples. Treatment with the demethylation agent 5-AZA can induceTPM2 expression in colorectal cancer cell lines. Reconstitution of TPM2 suppresses cell proliferation and migration in colorectal cancer cell lines, whereas the loss of TPM2 expression is associated with increased tumor proliferation and migration in vitro, which was accompanied by RhoA activation. In summary, our findings indicate that TPM2 appears to be commonly silenced by aberrant DNA methylation in colon cancer. TPM2 loss is associated with RhoA activation and tumor proliferation.
authors.affiliation: Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Colorectal Surgery, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, 56055, China.|Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Medicine II, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Colorectal Surgery, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, 56055, China.|Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zenghong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Colorectal Surgery, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, 56055, China.|Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.|Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. D4-100, Seattle, WA, 98109, USA.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. D4-100, Seattle, WA, 98109, USA.|Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.|Research and Development Service, VA Puget Sound Health Care System, Seattle, WA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kaz
authors.affiliation: Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Zihuan
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.|Department of Oncology, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dianke
authors.initials: D
authors.lastname: Chen
authors.affiliation: Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China.|Department of Pathology, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: Xinjuan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N. D4-100, Seattle, WA, 98109, USA. wgrady@fhcrc.org.|Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. wgrady@fhcrc.org.
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.affiliation: Department of Colorectal Surgery, the Sixth Affilated Hospital of Sun Yat-Sen University, Guangzhou, 56055, China. wjp@mail.sysu.edu.cn.|Gastrointestinal Institute, Sun Yat-Sen University, Guangzhou, China. wjp@mail.sysu.edu.cn.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000209:etiology*; D019175:DNA Methylation; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D014335:Tropomyosin / Q000235:genetics*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
chemical_list: C518659:TPM2 protein, human; D014335:Tropomyosin; D020742:rhoA GTP-Binding Protein
keywords: Colorectal cancer; DNA methylation; TPM2