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Somatic human ZBTB7A zinc finger mutations promote cancer progression

Oncogene volume 35, pages 3071–3078 (2016)Cite this article

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Abstract

We recently reported that ZBTB7A is a bona fide transcription repressor of key glycolytic genes and its downregulation in human cancer contributes to tumor metabolism. As reduced expression of ZBTB7A is found only in a subset of human cancers, we explored alternative mechanisms of its inactivation by mining human cancer genome databases. We discovered recurrent somatic mutations of ZBTB7A in multiple types of human cancers with a marked enrichment of mutations within the zinc finger domain. Functional characterization of the mutants demonstrated that mutations within the zinc finger region of ZBTB7A invariably resulted in loss of function. As a consequence, the glycolytic genes were markedly upregulated in cancer cells harboring ZBTB7A zinc finger mutation, leading to increased glycolysis and proliferation. Our study uncovers the loss-of-function mutation in ZBTB7A as a novel mechanism causing elevated glycolysis in human cancer, which carries important therapeutic implication.

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Acknowledgements

We are grateful to current and former members of the Yuan lab for experimental support, advice and helpful discussions. This work was supported in part by the Morningside Foundation and grants from NIH/NCI (R01CA085679, RO1CA167814 and RO1CA125144).

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Authors and Affiliations

  1. Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA

    X-S Liu, C Gerarduzzi, D E Choi, S Ganapathy & Z-M Yuan

  2. School of Life Science and Technology, ShanghaiTech University, Shanghai, 201203, China

    X-S Liu

  3. Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA

    Z Liu

  4. Departments of Medicine and Pathology, Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    P P Pandolfi

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  1. X-S Liu
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Correspondence to Z-M Yuan.

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Liu, XS., Liu, Z., Gerarduzzi, C. et al. Somatic human ZBTB7A zinc finger mutations promote cancer progression. Oncogene 35, 3071–3078 (2016). https://doi.org/10.1038/onc.2015.371

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  • DOI: https://doi.org/10.1038/onc.2015.371

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