Adipocyte p62/SQSTM1 Suppresses Tumorigenesis through Opposite Regulations of Metabolism in Adipose Tissue and Tumor

Publication date: 9 April 2018
Source:Cancer Cell, Volume 33, Issue 4
Author(s): Jianfeng Huang, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Elias A. Castilla, Timo D. Müller, Matthias H. Tschöp, Jorge Moscat, Maria T. Diaz-Meco
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.

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Huang et al. show in a prostate cancer mouse model that p62 loss in adipocytes leads to aggressive disease by increasing osteopontin secretion, which mediates tumor fatty acid oxidation and invasion. P62 deficiency also represses energy-consuming pathways in adipocytes, increasing nutrient availability for tumors.


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