title: Somatic human ZBTB7A zinc finger mutations promote cancer progression.
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.
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.|School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China.
authors.forename: X-S
authors.initials: XS
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gerarduzzi
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Choi
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ganapathy
authors.affiliation: Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: P P
authors.initials: PP
authors.lastname: Pandolfi
authors.affiliation: Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Z-M
authors.initials: ZM
authors.lastname: Yuan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006019:Glycolysis / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C485514:ZBTB7A protein, human