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- Title
Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate.
- Authors
Huang, Chun-Kai; Chang, Po-Hao; Kuo, Wen-Hung; Chen, Chi-Long; Jeng, Yung-Ming; Chang, King-Jen; Shew, Jin-Yuh; Hu, Chun-Mei; Lee, Wen-Hwa
- 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.
- Publication
Nature Communications, 2017, Vol 8, Issue 3, p14706
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/ncomms14706