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

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

Jianfeng Huang, Angeles Duran, Miguel Reina-Campos, Tania Valencia, Elias A Castilla, Timo D Müller, Matthias H Tschöp, Jorge Moscat, Maria T Diaz-Meco

Cancer Cell. 2018 Apr 9;33(4):770-784.e6.

PMID: 29634950

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248559	Osteopontin from mouse			Price

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