Tumor metastasis is the major cause of mortality from
cancer. Metabolic rewiring and the metastatic cascade are highly intertwined, co-operating to promote multiple steps of
cancer metastasis. Metabolites generated by
cancer cells influence the metastatic cascade, encompassing epithelial-mesenchymal transition (EMT), survival of
cancer cells in circulation, and metastatic colonization at distant sites. A variety of molecular mechanisms underlie the prometastatic effect of
tumor-derived metabolites, such as epigenetic deregulation, induction of
matrix metalloproteinases (
MMPs), promotion of
cancer stemness, and alleviation of oxidative stress. Conversely, metastatic signaling regulates expression and activity of rate-limiting metabolic
enzymes to generate prometastatic metabolites thereby reinforcing the
metastasis cascade. Understanding the complex interplay between metabolism and
metastasis could unravel novel molecular targets, whose intervention could lead to improvements in the treatment of
cancer. In this review, we summarized the recent discoveries involving metabolism and
tumor metastasis, and emphasized the promising molecular targets, with an update on the development of small molecule or biologic inhibitors against these aberrant situations in
cancer.