Mechanisms of induction of tumors by cholesterol and potential therapeutic prospects

Xi, Yang; Yani, Zhou; Mao, Jing; Wu, Yinhang; Hou, Xiaohui; Jing, Zhuang; Qi, Qi; Han, Shuwen

doi:10.1016/j.biopha.2021.112277

Cited by 16 publications

(7 citation statements)

References 99 publications

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“…Multiple studies suggested that lipids other than fatty acids, such as cholesterol, also play a key role in tumor progression, and the inhibition of cholesterol synthesis is detrimental to cancer cells ( 6 , 58 ). Cholesterol biosynthesis begins with the formation of acetoacetyl-CoA by the condensation of two molecules of acetyl coenzyme A through Acyl co-enzyme A-cholesterol acyltransferase (ACAT).…”

Section: Lipid Metabolism Reprogramming In Tumor Cells and Tumor Stro...mentioning

confidence: 99%

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

Wang

et al. 2022

Front. Oncol.

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Aberrant lipid metabolism is nonnegligible for tumor cells to adapt to the tumor microenvironment (TME). It plays a significant role in the amount and function of immune cells, including tumor-associated macrophages, T cells, dendritic cells and marrow-derived suppressor cells. It is well-known that the immune response in TME is suppressed and lipid metabolism is closely involved in this process. Immunotherapy, containing anti-PD1/PDL1 therapy and adoptive T cell therapy, is a crucial clinical cancer therapeutic strategy nowadays, but they display a low-sensibility in certain cancers. In this review, we mainly discussed the importance of lipid metabolism in the formation of immunosuppressive TME, and explored the effectiveness and sensitivity of immunotherapy treatment by regulating the lipid metabolism.

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Section: Lipid Metabolism Reprogramming In Tumor Cells and Tumor Stro...mentioning

confidence: 99%

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

Wang

et al. 2022

Front. Oncol.

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“…Inhibition of these pathways restores specific antitumor immunity. Thus, while cholesterol is a fundamental component of phospholipid bilayers, which enables membrane biogenesis and proliferation of cancer cells 59 , the activation of RORγ, consequent to lipid dysmetabolism, triggers a protumoral myelopoiesis that establishes immunosuppressive conditions in the host, facilitating both metastatic spread and seeding. Indeed, hypercholesterolemia induces the expression of PD-L1 in TAMs, IMs, and AMs (Fig.2e, f, Extended Data Fig.…”

Section: Discussionmentioning

confidence: 99%

RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression

Bleve,

Consonni,

Incerti

et al. 2023

Preprint

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Despite well-documented metabolic and hematopoietic alterations during tumor development1, the mechanisms underlying this crucial immunometabolic intersection have remained elusive. Of particular interest is the ligand-activated transcription factor retinoic acid-related orphan receptor 1 (RORC1/RORγ), whose activity is boosted by cholesterol metabolites2, acting as a modulator of cancer-related emergency myelopoiesis3, while hypercholesterolemia itself is associated with dysregulated myelopoiesis4,5. Here we show that both cancer growth and hypercholesterolemic diet can independently or cooperatively activate RORγ-dependent expansion of myeloid-derived suppressor cells (MDSCs) and M2 polarization of tumor-associated macrophages (TAMs), thereby supporting cancer spread. Moreover, we report that tumor development enhances the hepatic production of IL-1β and IL-6, which in turn promote upregulation of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, as we confirmed in models of fibrosarcoma, melanoma, colorectal (CRC), and lung cancer, as well as in CRC, non-small-cell lung cancer (NSCLC), breast (BRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract carcinoma (BTC) and pancreatic neuroendocrine tumor (PNET) patients. Importantly, lowering cholesterol levels prevents MDSC expansion and M2 TAM accumulation in a RORγ-dependent manner, unleashing specific anti-tumor immunity and improving the efficacy of anti-PD-1 immunotherapy. Overall, we identify RORγ as a novel sensor of lipid disorders in cancer bearers, bridging hypercholesterolemia and pro-tumor myelopoiesis.

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“…This epigenome affects histone modification and DNA methylation. 9,10 GM is an important component of cancer mediation as it metabolizes cholesterol, which in turn mediates epigenetic mechanisms. 11 The activity of histone deacetylases (HDACs) as a core epigenetic enzyme is inhibited by the butyrate, the microbiome metabolites.…”

Section: Introductionmentioning

confidence: 99%

“…GM provides environmental signals that modify host response to stimuli through the modification of host epigenome. This epigenome affects histone modification and DNA methylation 9,10 . GM is an important component of cancer mediation as it metabolizes cholesterol, which in turn mediates epigenetic mechanisms 11 .…”

Section: Introductionmentioning

confidence: 99%

The connection between epigenetics and gut microbiota‐current perspective

Yuan,

Tan,

Bajinka

et al. 2024

Cell Biochemistry & Function

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Both the epigenetic changes and gut microbiota (GM) have attracted a growing interest in establishing effective diagnostics and potential therapeutic strategies for a number of diseases. These disorders include metabolic, central nervous system‐related diseases, autoimmune, and gastrointestinal infections (GI). Despite the number of studies, there is no extensive review that connects the epigenetics modifications and GM as biomarkers that could confer effective diagnostics and confer treatment options. To this end, this review hopes to give detailed information on connecting the modifications in epigenetic and GM. An updated and detailed information on the connection between the epigenetics factors and GM that influence diseases are given. In addition, the review showed some associations between the epigenetics to the maternal GM and offspring health. Finally, the limitations of the concept and prospects into this new emerging discipline were also looked into. Although this review elucidated on the maternal diet and response to offspring health with respect to GM and epigenetic modifications, there still exist various limitations to this newly emerging discipline. In addition to integrating complementary multi‐omics data, longitudinal sampling will aid with the identification of functional mechanisms that may serve as therapeutic targets. To this end, this review gave a detailed perspective into harnessing disease diagnostics, prevention and treatment options through epigenetics and GM.

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Mechanisms of induction of tumors by cholesterol and potential therapeutic prospects

Cited by 16 publications

References 99 publications

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression

The connection between epigenetics and gut microbiota‐current perspective

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