Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review

Abstract

Esophageal cancer is of high importance to occurrence, development, and treatment resistance. As evidenced by recent studies, pathways (e.g., Wnt/β-catenin, AMPK, and Hippo) are critical to the proliferation, differentiation, and self-renewal of esophageal cancer. In addition, the above pathways play a certain role in regulating esophageal cancer and act as potential therapeutic targets. Over the past few years, the function of lipid metabolism in controlling tumor cells and immune cells has aroused extensive attention. It has been reported that there are intricate interactions between lipid metabolism reprogramming between immune and esophageal cancer cells, whereas molecular mechanisms should be studied in depth. Immune cells have been commonly recognized as a vital player in the esophageal cancer microenvironment, having complex crosstalk with cancer cells. It is increasingly evidenced that the function of immune cells in the tumor microenvironment (TME) is significantly correlated with abnormal lipid metabolism. In this review, the latest findings in lipid metabolism reprogramming in TME are summarized, and the above findings are linked to esophageal cancer progression. Aberrant lipid metabolism and associated signaling pathways are likely to serve as a novel strategy to treat esophageal cancer through lipid metabolism reprogramming.

SLC43A2 and NFκB signaling pathway regulate methionine/cystine restriction-induced ferroptosis in esophageal squamous cell carcinoma via a feedback loop

“…Our enrichment results also showed the fatty acid degradation and biosynthesis was regulated by methionine/cystine intake. It has been demonstrated that by regulating the level of fatty acid metabolism in esophageal cancer cells, it could lead to changes in inflammatory cell function in the tumor immune microenvironment and further affect the development and progression of esophageal cancer [ 68 ]. ACSL5 and ALAS2 were downregulated in MCR group, they were all involved in fatty acid metabolism and played different roles in cancer.…”

Editorial: Complexity of tumor microenvironment: A major culprit in cancer development

“…However, the detailed profiles of immune cell infiltration and differentially expressed genes (metabolic, immune-related, or others) in many cancers continue to be elucidated ( 7 , 16 , 17 ). Several metabolic factors have shown an association with pathogenesis and progression of various cancers ( 18 , 19 ) such as de novo lipid biosynthesis is a crucial regulator in the prostate cancer ( 20 – 22 ). An anecdotal observation metabolic health of the individuals may influence the prognosis and treatment of the cancers.…”