Salita Timothy, Rustam Yepy H, Mouradov Dmitri, Sieber Oliver M, Reid Gavin E
Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, VIC 3010, Australia.
Personalized Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Cancers (Basel). 2022 Jul 29;14(15):3714. doi: 10.3390/cancers14153714.
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.
脂质具有多样的结构,在膜稳态和生物能量代谢中具有多种调节功能,在介导功能性蛋白质-脂质和蛋白质-蛋白质相互作用中发挥作用,如在细胞信号传导和增殖过程中。越来越多的证据支持这样一种观点,即涉及细胞膜结构重塑、能量稳态变化以及癌症相关信号通路中信号传导的异常脂质代谢,在结直肠癌(CRC)的发生、发展和维持及其致瘤特性中起着关键作用。分析脂质组分析技术的最新进展使得能够全面鉴定脂质并对其进行结构表征,从而增进了我们对它们在肿瘤进展中所起作用的理解。然而,尽管我们在癌细胞代谢和脂质组学的理解方面取得了进展,但结直肠癌中关键的脂质相关变化尚未与Hanahan和Weinberg定义的公认的“癌症标志”明确关联起来。在这篇综述中,我们总结了突出重编程脂质代谢在结直肠癌中作用的最新发现,并利用这一不断增加的证据提出结直肠癌的八个与脂质代谢相关的标志,并强调它们的重要性以及与既定癌症标志的联系。