Leptin, locally secreted in the TME by both adipocytes and cancer-associated fibroblasts (CAFs) [43], has been shown to be involved in various steps of tumor invasion and metastasis through interaction with its Ob-R receptor expressed by cancer cells and activation of the downstream signaling pathway JAK-STAT3, PI3K/AKT and MAPK [29]. The gene discussed is AKT1; the disease is cancer.