title: ZBTB7A Suppresses Melanoma Metastasis by Transcriptionally Repressing MCAM.
abstract: The excessive metastatic propensity of melanoma makes it the most deadly form of skin cancer, yet the underlying mechanism of metastasis remains elusive. Here, mining of cancer genome datasets discovered a frequent loss of chromosome 19p13.3 and associated downregulation of the zinc finger transcription factor ZBTB7A in metastatic melanoma. Functional assessment of ZBTB7A-regulated genes identified MCAM, which encodes an adhesion protein key to melanoma metastasis. Using an integrated approach, it is demonstrated that ZBTB7A directly binds to the promoter and transcriptionally represses the expression of MCAM, establishing ZBTB7A as a bona fide transcriptional repressor of MCAM. Consistently, downregulation of ZBTB7A results in marked upregulation of MCAM and enhanced melanoma cell invasion and metastasis. An inverse correlation of ZBTB7A and MCAM expression in association with melanoma metastasis is further validated with data from analysis of human melanoma specimens.
  
  
  CONCLUSIONS
  Together, these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Liu
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Genet
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Haines
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Elie K
authors.initials: EK
authors.lastname: Mehanna
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Shaowei
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Hung-I Harry
authors.initials: HI
authors.lastname: Chen
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Warren Alpert Medical School, Brown University, Providence, Rhode Island.
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.affiliation: Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
authors.affiliation: Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts. zyuan@hsph.harvard.edu.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D000818:Animals; D001665:Binding Sites; D051929:CD146 Antigen / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012878:Skin Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D016335:Zinc Fingers
chemical_list: D051929:CD146 Antigen; D004268:DNA-Binding Proteins; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D014157:Transcription Factors; C485514:ZBTB7A protein, human; C117093:Zbtb7a protein, mouse