title: Functional characterization of Trip10 in cancer cell growth and survival.
abstract: BACKGROUND
  The Cdc42-interacting protein-4, Trip10 (also known as CIP4), is a multi-domain adaptor protein involved in diverse cellular processes, which functions in a tissue-specific and cell lineage-specific manner. We previously found that Trip10 is highly expressed in estrogen receptor-expressing (ER+) breast cancer cells. Estrogen receptor depletion reduced Trip10 expression by progressively increasing DNA methylation. We hypothesized that Trip10 functions as a tumor suppressor and may be involved in the malignancy of ER-negative (ER-) breast cancer. To test this hypothesis and evaluate whether Trip10 is epigenetically regulated by DNA methylation in other cancers, we evaluated DNA methylation of Trip10 in liver cancer, brain tumor, ovarian cancer, and breast cancer.
  
  
  METHODS
  We applied methylation-specific polymerase chain reaction and bisulfite sequencing to determine the DNA methylation of Trip10 in various cancer cell lines and tumor specimens. We also overexpressed Trip10 to observe its effect on colony formation and in vivo tumorigenesis.
  
  
  RESULTS
  We found that Trip10 is hypermethylated in brain tumor and breast cancer, but hypomethylated in liver cancer. Overexpressed Trip10 was associated with endogenous Cdc42 and huntingtin in IMR-32 brain tumor cells and CP70 ovarian cancer cells. However, overexpression of Trip10 promoted colony formation in IMR-32 cells and tumorigenesis in mice inoculated with IMR-32 cells, whereas overexpressed Trip10 substantially suppressed colony formation in CP70 cells and tumorigenesis in mice inoculated with CP70 cells.
  
  
  CONCLUSIONS
  Trip10 regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of Trip10 can either promote cell survival or cell death in a cell type-dependent manner.
authors.affiliation: Human Epigenomics Center, Department of Life Science, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Hsu
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Leu
authors.forename: Min-Jen
authors.initials: MJ
authors.lastname: Tseng
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Tzen-Yu
authors.initials: TY
authors.lastname: Kuo
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Yen
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Lai
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Hung
authors.forename: Wei-Sheng
authors.initials: WS
authors.lastname: Sun
authors.forename: Chien-Min
authors.initials: CM
authors.lastname: Chen
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.forename: Kun-Tu
authors.initials: KT
authors.lastname: Yeh
authors.forename: Pearlly S
authors.initials: PS
authors.lastname: Yan
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D002470:Cell Survival; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; C406285:TRIP10 protein, human; C485787:Trip10 protein, mouse