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TRIM24 links glucose metabolism with transformation of human mammary epithelial cells

Oncogene volume 34, pages 2836–2845 (2015)Cite this article

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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.

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Acknowledgements

We thank Abhinav Jain and Srikanth Appikonda for helpful discussions. Zeynep Coban and Kadir Akdemir for help with Bioinformatic analyses. Lindsey Minter and Joseph Taube for help with Xenograft experiments. This research is supported by grant RP100602 from the Cancer Prevention and Research Initiative of Texas to MCB, the Center for Cancer Epigenetics scholarship to KNT and in part by the MD Anderson Cancer Center Support Grant CA016672.

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Author notes

  1. T N Pathiraja

    Present address: 7Current address: Genome Institute of Singapore, Singapore.,

  2. T N Pathiraja and K N Thakkar: These authors contributed equally to this work.

Authors and Affiliations

  1. 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

    T N Pathiraja, K N Thakkar, S Jiang, S Stratton, Z Liu & M C Barton

  2. Department of Veterinary Medicine and Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Gagea

  3. Institute for Applied Cancer Science, the University of Texas MD Anderson Cancer Center, Houston, TX, USA

    X Shi, P K Shah & J Andersen

  4. Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA

    L Phan & M-H Lee

  5. Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA

    M Stampfer

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Correspondence to M C Barton.

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Pathiraja, T., Thakkar, K., Jiang, S. et al. TRIM24 links glucose metabolism with transformation of human mammary epithelial cells. Oncogene 34, 2836–2845 (2015). https://doi.org/10.1038/onc.2014.220

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