The macroenviromental control of cancer metabolism by p62

Metabolic reprogramming is a hallmark of cancer, but most studies focus on the molecular alterations in cancer cells and much less is known on the role of cancer metabolism, from a holistic perspective, for tumor initiation and progression. Increasing epidemiological evidence highlights the tremendous impact that cancer progression has on the host metabolism, especially in cachexia. However, how this benefits the tumor still is not completely understood. Here we review current studies on fatty acid oxidation in tumor cells as a potential therapeutic target in cancer, and how the redistribution of lipids from fat reservoirs to the cancer cell in the micro- and macro-environment impacts tumorigenesis by helping the tumor fulfill its energetic demands at the expense of fat. In this context, we also discuss the critical role of the signaling adaptor p62/Sequestosome 1(SQSTM1) in adipocytes in mediating tumor-induced fat reprograming and the feedback of adipose tissue on tumor aggressiveness via osteopontin and its potential implications in obesity-promoted cancer and fat cachexia. Collectively these studies highlight the importance of the symbiotic collaboration between adipose tissue and tumor to modulate the cancer metabolic fitness.