Reprogrammed Lipid Metabolism and the Lipid-Associated Hallmarks of Colorectal Cancer

SIMPLE SUMMARY: Colorectal cancer (CRC) is the third-most diagnosed cancer and the second-leading cause of cancer-related deaths worldwide. Limitations in early and accurate diagnosis of CRC gives rise to poor patient survival. Advancements in analytical techniques have improved our understanding of the cellular and metabolic changes occurring in CRC and potentiate avenues for improved diagnostic and therapeutic strategies. Lipids are metabolites with important biological functions; however, their role in CRC is poorly understood. Here, we provide an in-depth review of the recent literature concerning lipid alterations in CRC and propose eight lipid metabolism-associated hallmarks of CRC. ABSTRACT: Lipids have diverse structures, with multifarious regulatory functions in membrane homeostasis and bioenergetic metabolism, in mediating functional protein–lipid and protein–protein interactions, as in cell signalling and proliferation. An increasing body of evidence supports the notion that aberrant lipid metabolism involving remodelling of cellular membrane structure and changes in energy homeostasis and signalling within cancer-associated pathways play a pivotal role in the onset, progression, and maintenance of colorectal cancer (CRC) and their tumorigenic properties. Recent advances in analytical lipidome analysis technologies have enabled the comprehensive identification and structural characterization of lipids and, consequently, our understanding of the role they play in tumour progression. However, despite progress in our understanding of cancer cell metabolism and lipidomics, the key lipid-associated changes in CRC have yet not been explicitly associated with the well-established ‘hallmarks of cancer’ defined by Hanahan and Weinberg. In this review, we summarize recent findings that highlight the role of reprogrammed lipid metabolism in CRC and use this growing body of evidence to propose eight lipid metabolism-associated hallmarks of colorectal cancer, and to emphasize their importance and linkages to the established cancer hallmarks.