Zbtb7a suppresses melanoma metastasis by transcriptionally repressing mcam

Xue Song Liu, Matthew D. Genet, Jenna E. Haines, Elie K. Mehanna, Shaowei Wu, Hung I.Harry Chen, Yidong Chen, Abrar A. Qureshi, Jiali Han, Xiang Chen, David E. Fisher, Pier Paolo Pandolfi, Zhi Min Yuan

Research output: Contribution to journalArticle

20 Scopus citations

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. Implications: Together, these results uncover a previously unrecognized role of ZBTB7A in negative regulation of melanoma metastasis and have important clinical implications.

Original languageEnglish (US)
Pages (from-to)1206-1217
Number of pages12
JournalMolecular Cancer Research
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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    Liu, X. S., Genet, M. D., Haines, J. E., Mehanna, E. K., Wu, S., Chen, H. I. H., Chen, Y., Qureshi, A. A., Han, J., Chen, X., Fisher, D. E., Pandolfi, P. P., & Yuan, Z. M. (2015). Zbtb7a suppresses melanoma metastasis by transcriptionally repressing mcam. Molecular Cancer Research, 13(8), 1206-1217. https://doi.org/10.1158/1541-7786.MCR-15-0169