Figure 2.

The bidirectional interaction between cancer cells and macrophages regulated by CD36 receptor in promoting metastasis. Due to hypoxic conditions, cancer cells in tumour microenvironment (TME) increase the uptake of exogenous fatty acids for survival, energy source and rapid proliferation. Depending on the type of cancer, literatures have mentioned CD36 promotes metastasis, invasion and angiogenesis by activating the downstream GSK-3β/β-catenin, O-GlcNAcylation, AKR1C2, ERK1/2 and MMP28 signalling pathways. However, the recruitment of macrophage to TME and become tumour-associated macrophages (TAMs) is significant for cancer progression. TAM tends to have a higher level of FA uptake and accumulation via CD36, which accordingly enhance the fatty acid oxidation (FAO) of TAMs to generate more energy. This phenomenon also upregulates the lipid biosynthesis to produce more nitric oxide (NO) and reactive oxygen species (ROS) and secrete high level of immunosuppressive cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α) and more. The dynamic interaction between cancer cells and TAMs constantly favouring the tumour evasion and ultimately metastasis. NADPH, nicotinamide adenine dinucleotide phosphate; TAG, triacylglycerol; VEGF, vascular endothelial growth factor; MMPs, matrix metalloproteinase; PPARγ, peroxisome proliferator- activated receptor gamma; FABP4, fatty acid-binding protein; STAT3, signal transducer and activator of transcription 3; mTORC2, mammalian target of rapamycin complex 2.