Abstract
Lipid cell membrane composed of various distinct lipids and proteins act as a platform to assemble various signaling complexes regulating innumerous cellular processes which are strongly downregulated or altered in cancer cells emphasizing the still-underestimated critical function of lipid biomolecules in cancer initiation and progression. In this review, we outline the current understanding of how membrane lipids act as signaling hot spots by generating distinct membrane microdomains called rafts to initiate various cellular processes and their modulation in cancer phenotypes. We elucidate tangible drug targets and pathways all amenable to small-molecule perturbation. Ranging from targeting membrane rafts organization/reorganization to rewiring lipid metabolism and lipid sorting in cancer, the work summarized here represents critical intervention points being attempted for lipid-based anticancer therapy and future directions.
Highlights
Lewis Thomas in the Lives of a Cell [1] underscored the ramifications rendered by the variety of lipids and their structural platforms
The quest for targeting cancer using varied chemical and genetic approaches still is faced with enormous hurdles and generates an unmet need to develop therapeutic approaches inspired by careful inspection of modulated cancer cell attributes
One of the aspects gaining considerable attention recently has been the altered lipid repertoire of cancer cells leading to modulated membrane-dependent cellular processes including membrane organization and cellular signaling, strongly contributing to tumor growth and metastasis and understanding the underlying mechanism behind the same to elucidate potentially novel targets and pathways against cancer
Summary
Lewis Thomas in the Lives of a Cell [1] underscored the ramifications rendered by the variety of lipids and their structural platforms. MAGL along with hormone sensitive lipase hydrolyzes triglycerides, stored in adipocytes and other cells to free fatty acids, which act as a source of energy [10]. Lipids fulfill many critical requirements in the cell including composing membrane bilayer, storing energy due to their reduced state, acting as first and second messengers in signal transduction, providing functional implementations of membrane-proteins structure and function, and recognition processes. In line with the increasing evidence elucidating the role of membrane lipids in regulating numerous cellular functions, they have emerged as attractive molecular targets wherein therapies modulating membrane lipids structures and localization could be developed to control molecular events including changes in cell signaling, membrane protein function, localization, and gene expression related to various pathological states—the so-called “membrane-lipid therapy” [16, 17]
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