Abstract
Colorectal cancer (CRC) to date still ranks as one of the deadliest cancer entities globally, and despite recent advances, the incidence in young adolescents is dramatically increasing. Lipid metabolism has recently received increased attention as a crucial element for multiple aspects of carcinogenesis and our knowledge of the underlying mechanisms is steadily growing. However, the mechanism how fatty acid metabolism contributes to CRC is still not understood in detail. In this review, we aim to summarize our vastly growing comprehension and the accompanied complexity of cellular fatty acid metabolism in CRC by describing inputs and outputs of intracellular free fatty acid pools and how these contribute to cancer initiation, disease progression and metastasis. We highlight how different lipid pathways can contribute to the aggressiveness of tumors and affect the prognosis of patients. Furthermore, we focus on the role of lipid metabolism in cell communication and interplay within the tumor microenvironment (TME) and beyond. Understanding these interactions in depth might lead to the discovery of novel markers and new therapeutic interventions for CRC. Finally, we discuss the crucial role of fatty acid metabolism as new targetable gatekeeper in colorectal cancer.
Highlights
Combined efforts in the field of colorectal cancer (CRC) have tremendously advanced the understanding, prognosis and treatment of this deadly disease over the past decades
With respect to CRC, Zaytseva et al very recently highlighted the importance of lipid dysregulation and its implications as targets for future therapies suggesting fatty acid metabolism could be exploited as a potent vulnerability [22]
Observed alterations are accompanied by elevated transcripts of lipogenic enzymes as fatty acid synthase (FASN) and FADS2 and the described signature could even be recapitulated in an APC mouse model [73]
Summary
Combined efforts in the field of colorectal cancer (CRC) have tremendously advanced the understanding, prognosis and treatment of this deadly disease over the past decades. In comparison to proteins and nucleic acids, lipid metabolism has received less attention, but lately the reliance of cancer cells on lipid-associated pathway dysregulation has been considered yet another crucial driver of malignant transformation [17]. These complex changes in lipid metabolism where recently discussed by Molendijk et al, who describe lipid metabolism as an essential part in multiple aspects of carcinogenesis by regulating the well-described hallmarks of cancer [18]. With respect to CRC, Zaytseva et al very recently highlighted the importance of lipid dysregulation and its implications as targets for future therapies suggesting fatty acid metabolism could be exploited as a potent vulnerability [22]. We highlight the role of lipid metabolism in cell communication and crosstalk within the tumor microenvironment
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