title: Histone deacetylase (HDAC) 10 suppresses cervical cancer metastasis through inhibition of matrix metalloproteinase (MMP) 2 and 9 expression.
abstract: Aberrant expression of histone deacetylases (HDACs) is associated with carcinogenesis. Some HDAC inhibitors are widely considered as promising anticancer therapeutics. A major obstacle for development of HDAC inhibitors as highly safe and effective anticancer therapeutics is that our current knowledge on the contributions of different HDACs in various cancer types remains scant. Here we report that the expression level of HDAC10 was significantly lower in patients exhibiting lymph node metastasis compared with that in patients lacking lymph node metastasis in human cervical squamous cell carcinoma. Forced expression of HDAC10 in cervical cancer cells significantly inhibited cell motility and invasiveness in vitro and metastasis in vivo. Mechanistically, HDAC10 suppresses expression of matrix metalloproteinase (MMP) 2 and 9 genes, which are known to be critical for cancer cell invasion and metastasis. At the molecular level, HDAC10 binds to MMP2 and -9 promoter regions, reduces the histone acetylation level, and inhibits the binding of RNA polymerase II to these regions. Furthermore, an HDAC10 mutant lacking histone deacetylase activity failed to mimic the functions of full-length protein. These results identify a critical role of HDAC10 in suppression of cervical cancer metastasis, underscoring the importance of developing isoform-specific HDAC inhibitors for treatment of certain cancer types such as cervical squamous cell carcinoma.
authors.affiliation: From the Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, School of Life Science and Technology, Tongji University, Shanghai 200092, China and.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Song
authors.forename: Songcheng
authors.initials: S
authors.lastname: Zhu
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002465:Cell Movement; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C447828:HDAC10 protein, human; D006655:Histone Deacetylases
keywords: Cell Invasion; Cell Migration; Histone Deacetylase; Matrix Metalloproteinase (MMP); Metastasis
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