Figure 16.

The functional activity of tumor suppressors and oncogenes may be cell-type and compartment specific: HIF1a as a key example. Here, we have shown that activated HIF1a behaves as a tumor promoter in cancer-associated fibroblasts (CAFs) and as a tumor suppressor in epithelial cancer cells. Thus, tumor suppressor or oncogenic activity may not be an intrinsic property of a given molecule per se, but where it is expressed may determine the functional consequences and clinical outcome. As such, the functional activity of “classic” tumor suppressors and oncogenes is compartment and cell-type specific. Horizontal arrows indicate the presumed direction of energy transfer (via Recycled Nutrients) based on autophagy induced by the expression of activated HIF1a. HIF1⁺, denotes HIF1-alpha activation/stabilization.