Peking University People's Hospital, Qingdao; Women and Children's Hospital, QINGDAO UNIVERSITY, Qingdao, 266111, China.
Medical Laboratory Center, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266035, China.
Oncogene. 2024 Nov;43(45):3277-3290. doi: 10.1038/s41388-024-03161-7. Epub 2024 Sep 16.
As two diseases with rapidly increasing incidence, the molecular linkages between obesity and breast cancer (BC) are intriguing. Overall, obesity may be a negative prognostic factor for BC. Single-cell RNA-sequencing (scRNA-seq) was performed on tumor tissues from 6 obese and non-obese BC patients. With 48,033 cells analyzed, we found heterogeneous tumor epithelium and microenvironment in these obese and lean BC patients. Interestingly, the obesity-associated epithelial cells exhibited specific expression signatures which linked tumor growth and hormone metabolism in BC. Notably, one population of obesity-specific macrophage up-regulated the nuclear receptor subfamily 1 group H member 3 (NR1H3), which acted a transcription factor and regulated FABP4 expression through its interaction with the DNA of SREBP1, and further increased the proliferation of tumor cells in BC. Using single-cell signatures, our study illustrate cell diversity and transcriptomic differences in tumors from obese and non-obese BC patients, and sheds light on potential molecular link between lipid metabolism and BC.
肥胖和乳腺癌（BC）是两种发病率迅速上升的疾病，它们之间的分子联系很有趣。总的来说，肥胖可能是 BC 的一个负面预后因素。对 6 名肥胖和非肥胖的 BC 患者的肿瘤组织进行了单细胞 RNA 测序（scRNA-seq）。分析了 48033 个细胞，我们发现这些肥胖和瘦弱的 BC 患者的肿瘤上皮细胞和微环境存在异质性。有趣的是，与肥胖相关的上皮细胞表现出特定的表达特征，这些特征将 BC 中的肿瘤生长和激素代谢联系起来。值得注意的是，肥胖特异性巨噬细胞的一个群体上调了核受体亚家族 1 组 H 成员 3（NR1H3），它作为转录因子通过与 SREBP1 的 DNA 相互作用来调节 FABP4 的表达，并进一步增加了 BC 中肿瘤细胞的增殖。利用单细胞特征，我们的研究说明了肥胖和非肥胖的 BC 患者肿瘤中的细胞多样性和转录组差异，并揭示了脂代谢和 BC 之间潜在的分子联系。
