脂肪细胞 p62/SQSTM1 通过对脂肪组织和肿瘤代谢的相反调节抑制肿瘤发生。
Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor.
机构信息
Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Sanford Burnham Prebys Graduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Cancer Cell. 2018 Apr 9;33(4):770-784.e6. doi: 10.1016/j.ccell.2018.03.001.
Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells in vivo, independently of dietary contributions, is a major gap in the field. Here we used a prostate cancer (PCa) mouse model in which the signaling adaptor p62/Sqstm1 is selectively inactivated in adipocytes. p62 loss in adipocytes results in increased osteopontin secretion, which mediates tumor fatty acid oxidation and invasion, leading to aggressive metastatic PCa in vivo. Furthermore, p62 deficiency triggers in adipocytes a general shutdown of energy-utilizing pathways through mTORC1 inhibition, which supports nutrient availability for cancer cells. This reveals a central role of adipocyte's p62 in the symbiotic adipose tissue-tumor collaboration that enables cancer metabolic fitness.
肥胖是癌症的一个主要危险因素。然而，在不考虑饮食贡献的情况下，体内脂肪细胞和肿瘤细胞之间的串扰尚不清楚，这是该领域的一个主要空白。在这里，我们使用了一种前列腺癌（PCa）小鼠模型，在该模型中，信号适配器 p62/Sqstm1 选择性地在脂肪细胞中失活。脂肪细胞中 p62 的缺失导致骨桥蛋白分泌增加，这介导了肿瘤脂肪酸氧化和侵袭，导致体内侵袭性转移性 PCa。此外，p62 的缺乏通过抑制 mTORC1 在脂肪细胞中触发能量利用途径的全面关闭，从而为癌细胞提供营养物质的可用性。这揭示了脂肪细胞中 p62 在共生脂肪组织-肿瘤协作中发挥的核心作用，这种协作使癌细胞具有代谢适应性。
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