Abstract
Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We reviewed the major lipid dysfunctions occurring during tumor development, as determined using systems biology approaches. In it, we provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. Finally, we summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression.
Highlights
Metabolic reprogramming is firmly established as a hallmark of cancer.[1]
Content, especially cholesteryl ester, is mobilized by pancreatic cancer cells under a restricted cholesterol-rich low-density lipoprotein (LDL) supply[14] and limiting LDL uptake reduces the oncogenic properties of pancreatic cancer cells and rendered them more sensitive to cytotoxic drugs.[14]
Inhibitor agents directed against lipogenic enzymes (FASN, ATP citrate lyase (ACLY) and acetyl-CoA carboxylase (ACC)) have been the subject of numerous studies; and their efficacy as anticancer therapies have been proven in various preclinical models of carcinogenesis (Table 1).[110,111,112]
Summary
Many human diseases, including metabolic, immune and central nervous system disorders, as well as cancer, are the consequence of an alteration in lipid metabolic enzymes and their pathways. This illustrates the fundamental role played by lipids in maintaining membrane homeostasis and normal function in healthy cells. We provide detailed insight into the essential roles exerted by specific lipids in mediating intracellular oncogenic signaling, endoplasmic reticulum stress and bidirectional crosstalk between cells of the tumor microenvironment and cancer cells. We summarize the advances in ongoing research aimed at exploiting the dependency of cancer cells on lipids to abolish tumor progression. Oncogenesis (2016) 5, e189; doi:10.1038/oncsis.2015.49; published online 25 January 2016
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