title: TET1 partially mediates HDAC inhibitor-induced suppression of breast cancer invasion.
abstract: Histone deacetylases (HDACs) are important in chromatin remodeling and epigenetic regulation of gene expression. Histone deacetylase inhibitors (HDACi) have highly effective anti-metastatic and anti-angiogenic activity in various types of cancer, while the molecular mechanisms involved in this process are not fully understood. In the present study, trichostatin A (TSA), a HDACi, was found to suppress MCF-7 breast carcinoma cell invasion and upregulate TET1 expression in a dose-dependent manner. TET1, a dioxygenase involved in cytosine demethylation, is downregulated during breast cancer progression. TET1 knockdown in MCF-7 cells facilitates cell invasion, inhibits the expression of tissue inhibitors of metalloproteinase 2/3 (TIMP2/3) and promotes matrix metalloproteinases (MMP) 2/9 transcriptional activity. Importantly, TET1 depletion impaired the inhibitory effect of TSA on breast cancer cell invasion. Together, these results illustrated a mechanism by which TET1 partially mediates HDACi elicited suppression of breast cancer invasion.
authors.affiliation: Department of Orthopedics, Central Hospital of Jingzhou, Hubei 434100, P.R. China.
authors.forename: Hou-Gen
authors.initials: HG
authors.lastname: Lu
authors.affiliation: Department of Medical Oncology, Shanghai Changzheng Hospital, Shanghai 200070, P.R. China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhan
authors.affiliation: Department of Orthopedics, Central Hospital of Jingzhou, Hubei 434100, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.affiliation: The First Affiliated Hospital of Xin‑Xiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Rui-Ying
authors.initials: RY
authors.lastname: Qin
authors.affiliation: The First Affiliated Hospital of Xin‑Xiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Yan
authors.affiliation: The First Affiliated Hospital of Xin‑Xiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Zhen-Jiang
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Orthopaedics Hospital of Nanyang, Nanyang, Henan 473003, P.R. China.
authors.forename: Gui-Chao
authors.initials: GC
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Xin‑Xiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Gui-Qin
authors.initials: GQ
authors.lastname: Li
authors.affiliation: Shanghai Hengrui Pharmaceutical Co., Ltd, Shanghai 20035, P.R. China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Shanghai Xuhai Biological Technology Co., Ltd, Shanghai 20032, P.R. China.
authors.forename: Xing-Liang
authors.initials: XL
authors.lastname: Li
authors.affiliation: Shanghai Xuhai Biological Technology Co., Ltd, Shanghai 20032, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Biotechnology, College of Life Sciences, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Surgery, Shanghai Tongren Hospital of Changning, Shanghai 200050, P.R. China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000502:physiology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D009361:Neoplasm Invasiveness; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011518:Proto-Oncogene Proteins; C560823:TIMP2 protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019716:Tissue Inhibitor of Metalloproteinase-2; C012589:trichostatin A; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9