Fig. 1.

Cancer metabolic plasticity contributes to metastatic disease. (A) Genetic mutations and epigenetic alterations in combination establish unique populations of tumour-initiating cells (TICs). Only certain TICs take advantage of the surrounding cells that constitute the tumour microenvironment (TME), such as vascular cells, cancer-associated fibroblasts (CAFs) and adipocytes, as well as their systemic environment, to exchange and hijack metabolites (shown in green) that support TIC survival. TICs hijack metabolites while egressing out of the primary lesion, thereby becoming metastasis-initiating cells (MICs). (B) As metastatic cells reach different distant organs via the vasculature, they adopt unique metabolic states and engage in further metabolic crosstalk with the (C) metastatic niches that form, for example, in the bone, lungs, liver and brain, ultimately supporting their survival. Tumour cells also secrete metastasis-promoting exosomes (yellow) that contain various proteins and RNAs that contribute to establish distant pro-metastatic niches.