The cell cycle regulator 14-3-3? opposes and reverses cancer metabolic reprogramming.

ABSTRACT: Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3? regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3? opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3? demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3? expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3? is an important regulator of tumour metabolism, and loss of 14-3-3? expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3? in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.

SUBMITTER: Phan L 

PROVIDER: S-EPMC4507299 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature