title: TRIM24 links glucose metabolism with transformation of human mammary epithelial cells.
abstract: Tripartite motif 24 protein (TRIM24) is a plant homeodomain/bromodomain histone reader, recently associated with poor overall survival of breast-cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24 iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24 iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24 iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancer.
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: T N
authors: TN
authors: Pathiraja
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: K N
authors: KN
authors: Thakkar
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Jiang
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: S
authors: S
authors: Stratton
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Z
authors: Z
authors: Liu
authors: Department of Veterinary Medicine and Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M
authors: M
authors: Gagea
authors: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: X
authors: X
authors: Shi
authors: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: P K
authors: PK
authors: Shah
authors: Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: L
authors: L
authors: Phan
authors: Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M-H
authors: MH
authors: Lee
authors: Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: J
authors: J
authors: Andersen
authors: Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors: M
authors: M
authors: Stampfer
authors: Department of Biochemistry and Molecular Biology, Center for Cancer Epigenetics, Center for Stem Cell and Developmental Biology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: M C
authors: MC
authors: Barton
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005947:Glucose / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude
chemical_list: D002352:Carrier Proteins; C555317:TRIM24 protein, human; D005947:Glucose