Give an illustrative example, leptin released into ATME by white adipocytes can blind to the leptin receptor which is highly abundant in many tumors, then synergize with plenty of different oncogenes, cytokines, and growth factors by impacting the JAK-2/STAT, PI3K/AKT-1, and MAPK/ ERK1/2 signaling pathways.248,249 Second, it has been proved that adipose tissue accelerates cancer development and enhances tumor resistance to chemotherapy or immunotherapy through impinge on immune cells in the microenvironment. The gene discussed is LEP; the disease is cancer.