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Nat Commun. 2017 Mar 10;8:14706. doi: 10.1038/ncomms14706.

Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate.

Author information

1
Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
2
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
3
Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
4
Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
5
Department of Pathology, National Taiwan University Hospital, Taipei 100, Taiwan.
6
Cheng Chin General Hospital, Taichung 407, Taiwan.
7
Graduate Institute of New Drug Development, China Medical University, Taichung 404, Taiwan.

Abstract

Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitro and in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.

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