Abstract
Lipid metabolism disorder is related to an increased risk of tumorigenesis and is involved in the rapid growth of cancer cells as well as the formation of metastatic lesions. Epidemiological studies have demonstrated that low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL) are closely associated with breast cancer, colorectal cancer, pancreatic cancer, and other malignancies, suggesting that LDL and ox-LDL play important roles during the occurrence and development of cancers. LDL can deliver cholesterol into cancer cells after binding to LDL receptor (LDLR). Activation of PI3K/Akt/mTOR signaling pathway induces transcription of the sterol regulatory element-binding proteins (SREBPs), which subsequently promotes cholesterol uptake and synthesis to meet the demand of cancer cells. Ox-LDL binds to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 36 (CD36) to induce mutations, resulting in inflammation, cell proliferation, and metastasis of cancer. Classic lipid-lowering drugs, statins, have been shown to reduce LDL levels in certain types of cancer. As LDL and ox-LDL play complicated roles in cancers, the potential therapeutic effect of targeting lipid metabolism in cancer therapy warrants more investigation.
Highlights
Cholesterol is an indispensable component of life, and the intracellular cholesterol levels are maintained through a series of factors, including cholesterol synthesis, uptake, efflux, esterification, metabolism, and transportation [1]
Studies have shown that inhibition of mevalonate pathway can down-regulate the expression of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) isoprenyls, the isoprenyl group is critical in modifying G proteins involved in cancer cell proliferation, migration, and survival [5]
The relationship between low plasma low-density lipoprotein (LDL)-C levels and cancer can be explained by increased uptake of cholesterol from plasma by malignant cells to meet their own proliferation needs
Summary
Cholesterol is an indispensable component of life, and the intracellular cholesterol levels are maintained through a series of factors, including cholesterol synthesis, uptake, efflux, esterification, metabolism, and transportation [1]. LDL-C can promote the proliferation of pancreatic cancer cells by activating the STAT3 pathway and upregulating the levels of oncogenes such as Bcl-2, Bcl-xL, survivin controlled by this transcription factor in pancreatic cancer cells [49] These findings suggest that LDLR can be a novel metabolic target in limiting patients progression [114, 115]. Because of the lack of LDLR feedback regulation, prostate cells obtain more essential fatty acids and increase prostaglandin 2 synthesis, leading to uncontrolled growth of prostate cancer cells [133] These studies suggest that prostate cancer may rely on cholesterol for metabolism and that low levels of LDL in cancer reflect the highly invasive nature of tumors. Statins reduce mortality and the risk of prostate-specific antigen (PSA) recurrence in a dose-dependent manner after prostatectomy
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