Metabolic Reprogramming in Cancer: the bridge that connects intracellular stresses and cancer behaviors

We outline in this perspective a novel framework for cancer study from the angle of stress-induced metabolic reprogramming. The driving question is: what may dictate the same or highly similar evolutionary trajectory across different cancers, consisting of cell proliferation, drug resistance, migration and metastasis? We have observed that cancer and cancer-forming cells are under a persistent intracellular alkaline stress, due to chronic inflammation and local iron overload. A wide range of reprogrammed metabolisms (RMs) are induced to keep the intracellular pH within a livable range for survival. Different from the normal metabolisms that have been optimized over millions of years of evolution, some RMs may generate products that are difficult to remove; hence the host cells must find novel ways to rid of them in a sustained and timely manner to keep the life-saving RMs going. We discuss how such adaptive measures may lead to a variety of cancerous behaviors; and propose an RM-based model as a new framework for studying cancer.