FIGURE 8.

Molecular mechanisms of exogenous lysophosphatidylcholines (lysoPCs)‐inhibited lung cancer cell proliferation. Exogenous lysoPC reprograms lipid metabolisms by increasing the accumulation of fatty acids (FA) and activating acyl‐CoA‐dominated metabolic mode under the control and regulation of long‐chain acyl‐coenzyme A synthases 5 (ACSL5). LysoPC up‐regulates the expression of ACSL5 and activates the ACSL5‐oriented lipid metabolism by promoting the phosphorylation of phosphoinositide 3‐kinase (PI3K)/mTOR and Ras/ERK signal pathways. ACSL5 plays a decisive role in the process during which lysoPC alters mitochondrial morphology and function as well as reactive oxygen species (ROS) over‐production. Exogenous lysoPC inhibited lung cancer cell proliferation by promoting ACSL5, leading to the disorder of FA degradation and metabolism, mitochondrial dysfunctions and reprogramming of ACSL5/PI3K/ERK‐regulated triacylglycerol (TAG) metabolism. Multi‐dimensions, layers and interactions of intracellular factors and signal pathways consist of a complex regulation of lung cancer cell sensitivity to lysoPC, evidenced by inhibition of involved signal pathways