1. Adipocyte p62/SQSTM1 suppresses tumorigenesis through opposite regulations of metabolism in adipose tissue and tumor
- Author
-
Miguel Reina-Campos, Jianfeng Huang, Elias A. Castilla, Tania Valencia, Timo D. Müller, Matthias H. Tschöp, Maria T. Diaz-Meco, Jorge Moscat, and Angeles Duran
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Adipose tissue ,mTORC1 ,Biology ,medicine.disease_cause ,Article ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Prostate cancer ,Sequestosome 1 ,Cell Line, Tumor ,Adipocyte ,Sequestosome-1 Protein ,medicine ,Animals ,Humans ,Obesity ,Osteopontin ,education ,education.field_of_study ,Carnitine O-Palmitoyltransferase ,Fatty Acids ,Prostatic Neoplasms ,Cell Biology ,Prognosis ,medicine.disease ,Cpt1 ,Cancer ,Fatty Acid Oxidation ,Metabolic Reprogramming ,P62 ,Prostate ,Sequestosome-1 ,Cell Transformation, Neoplastic ,030104 developmental biology ,Adipose Tissue ,Oncology ,chemistry ,Cancer cell ,Cancer research ,biology.protein ,Energy Metabolism ,Carcinogenesis ,Neoplasm Transplantation - Abstract
Obesity is a leading risk factor for cancer. However, understanding the crosstalk between adipocytes and tumor cells invivo, 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 invivo. 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.
- Published
- 2018