Figure 2.

Metabolic interactions between tumours and their microenvironment (TME). Interactions between the tumour, the TME, and other environmental factors are represented in this figure. Solid arrows indicate demonstrated interactions, while dashed lines with question marks designate putative ones. Nonautonomous metabolic changes in the TME can affect both the TME and the tumour and are generated through various means. High levels of dietary sugar promote tumour growth and induce systemic insulin resistance in the TME. Tumours can also perturb TME insulin signalling by the secretion of an insulin-signalling antagonist, ImpL2. Autophagy in the TME promotes tumour growth through the recycling of amino acids from the TME into the tumour. Expression of the amino acid transporter slif in the tumour is necessary for this protumour effect. TME autophagy can be triggered by tumour-derived ROS and may also be driven by cytokine signalling or direct competition with the tumour for nutrients. Both, autophagy and impaired insulin signalling can contribute to tissue wasting and cancer cachexia. The causes of wasting in the TME and the effects of wasting in these tissues are an increasing research focus. However, the effects of TME wasting on the tumour remain an open question.