Fig. 1

Adipocytes represent a central player in the creation of the metabolic tumor microenvironment in the omentum during ovarian cancer metastasis. Adipocytes are reprogrammed into cancer-associated adipocytes by cancer-derived mediators. These activated adipocytes release a wealth of lipids and various adipokines, including IL-6, IL-8, MCP-1, and TIMP-1, which contribute to the establishment of the omental metastatic niche for ovarian cancer. FABP4, which is an intracellular chaperone for free fatty acids, regulates lipolysis in adipocytes and β-oxidation in ovarian cancer cells, and plays a crucial role in the interaction of ovarian cancer cells with adipocytes, promoting omental metastasis. In addition, omental adipocytes induce the calcium-dependent activation and autophosphorylation of SIK2 in ovarian cancer cells and activate cancer cell proliferation through the PI3K/AKT pathway. SIK2 can increase ovarian cancer cell fatty acid oxidation by augmenting AMPK-induced ACC phosphorylation and activating CPT1 during peritoneal disseminated metastasis. Thus, the highly orchestrated crosstalk between ovarian cancer cells and omental adipocytes induces metabolic synergies by reprogramming fatty acid metabolism and tumor-promoting signaling pathways that enhance the proliferation, invasion, and metastatic progression of ovarian cancer cells with specific metastatic tropism for the omentum