Lipid metabolism reprogramming in colorectal cancer

Abstract

The hallmark feature of metabolic reprogramming is now considered to be widespread in many malignancies, including colorectal cancer (CRC). Of the gastrointestinal tumors, CRC is one of the most common with a high metastasis rate and long insidious period. The incidence and mortality of CRC has increased in recent years. Metabolic reprogramming also has a significant role in the development and progression of CRC, especially lipid metabolic reprogramming. Many studies have reported that lipid metabolism reprogramming is similar to the Warburg effect with typical features affecting tumor biology including proliferation, migration, local invasion, apoptosis, and other biological behaviors of cancer cells. Therefore, studying the role of lipid metabolism in the occurrence and development of CRC will increase our understanding of its pathogenesis, invasion, metastasis, and other processes and provide new directions for the treatment of CRC. In this paper, we mainly describe the molecular mechanism of lipid metabolism reprogramming and its important role in the occurrence and development of CRC. In addition, to provide reference for subsequent research and clinical diagnosis and treatment we also review the treatments of CRC that target lipid metabolism.

UHPLC-HRMS-Based Multiomics to Explore the Potential Mechanism and Biomarkers for Colorectal Cancer

“…Hence, changes in FA sources may determine the phospholipid composition of cell membranes and thus indirectly affect membrane function (33,34). Reactivating de novo synthesis of FA is the main pathway for CRC cells to obtain FA (35). In our results, the shared 10 FA we found in CRC cells at different stages were mainly involved in linoleic acid metabolism and carnitine metabolism.…”

Monitoring Metabolic Changes in Response to Chemotherapies in Cancer with Raman Spectroscopy and Metabolomics

“…Thus, the downregulation of proliferative signaling could reprogram the cell’s lipid usage and lead to lipid storage. Lipid droplets have been shown to accumulate under stress conditions in CRC and can contribute to chemoresistance. , We also aimed to quantitatively compare the metabolites identified with RS (Figure a) with those obtained with LC–MS (Figure b) and specifically represent cell membrane phospholipids (722 cm –1 ), DNA bases (783 cm –1 ), arginine (991 cm –1 ), and triglycerides (1300 cm –1 ) with equivalent representative species from the LC–MS data. − We find that for RS and LC–MS, the trends in metabolites for the various sample groups are generally in agreement, which not only shows that these two approaches are complimentary but also highlights the strengths and limitations of each method. RS is a low-cost extraction-free approach that allows rapid measurement of cells at the single cell level capturing heterogeneities in treatment response within individual cells with high sensitivity.…”

“…Lipid droplets have been shown to accumulate under stress conditions in CRC and can contribute to chemoresistance. 45,70 We also aimed to quantitatively compare the metabolites identified with RS (Figure 5a) with those obtained with LC−MS (Figure 5b) and specifically represent cell membrane phospholipids (722 cm −1 ), DNA bases (783 cm −1 ), arginine (991 cm −1 ), and triglycerides (1300 cm −1 ) with equivalent representative species from the LC−MS data. 35−39 We find that for RS and LC−MS, the trends in metabolites for the various sample groups are generally in agreement, which not only shows that these two approaches are complimentary but also highlights the strengths and limitations of each method.…”

“…We then identified 32 statistically significant peaks in RS using a Student’s t -test with the false discovery rate correction and corresponding metabolites that differentiated OX-treated cells from untreated control (Figure e); 28 of these metabolites decreased in the treatment group and 4 metabolites increased. To associate RS spectral data with specific metabolites and metabolite classes, we referred to the cited literature in Table that reports well-established RS peaks for key metabolites. − Tentative peak assignments were narrowed down based on literature on metabolites that are impacted in human CRC and cellular metabolites that change in response to treatment; these literature evidence supported the assigned Raman peaks to the metabolites we have listed. ,− As each RS peak arises from vibrational modes within a functional group, a specific peak is not exclusive to a metabolite. Therefore, our tentative peak assignments represent the most plausible major metabolites that contribute to these peaks.…”

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer

“…Lipids have vital physiological functions. In addition to being the main components of cell membranes, they are involved in the synthesis and regulation of biological macromolecules and serve as second messengers and energy reservoirs [ 25 ]. Previous studies indicated that phospholipids levels increase in CRC tissue, possibly due to increased synthesis of plasma membranes in rapidly proliferating cancer cells [ 26 ].…”