The emerging role of 27-hydroxycholesterol in cancer development and progression: An update

Jasim, Saade Abdalkareem; Kzar, Hamzah H.; Hamad, Mohammed Haider; Ahmad, Irfan; Al‐Gazally, Moaed E.; Ziyadullaev, Shukhrat; Sivaraman, R.; Jawad, Mohammed Abed; Hammid, Ali Thaeer; Oudah, Khulood H.; Karampoor, Sajad; Mirzaei, Rasoul

doi:10.1016/j.intimp.2022.109074

Cited by 26 publications

(15 citation statements)

References 219 publications

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“…In the TME, 27-HC is mainly derived from macrophages and endothelial cells. 27-HC inhibits the uptake and synthesis of FA and cholesterol by inhibiting the SREBP pathway and activating the liver X receptor (LXR) pathway 106 . In contrast, 27-HC can competitively inhibit the effect of estrogen because of its selective estrogen receptor (ER) regulatory function and promotes the proliferation of high-ER-expressing tumor cells, such as breast and ovarian cancer cells 107 .…”

Section: Landscape Of Abnormal Lipid Metabolism In Tumorsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.

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Section: Landscape Of Abnormal Lipid Metabolism In Tumorsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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“…Strikingly, 27HC stimulates the proliferation of mouse melanoma cells by activating estrogen receptor alpha (ERa) and triggering the AKT and MAPK pathways 37 . Compelling research into potential therapeutic strategies targeting bile acid metabolism can be found in breast cancer research 38,39 . For example, pharmacologic inhibition of CYP27A1 improved the efficacy of anti-PD-1 treatment and decreased metastatic breast cancer growth in mice 40 .…”

Section: Enrichment Of Metabolism Pathways In Cd8 + Til In Melanomamentioning

confidence: 99%

Re-evaluating the melanoma TIL compartment and its unexpected spectrum of exhausted and functional T cells

Cameron

Richardson

Golden

et al. 2023

Preprint

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Significant heterogeneity exists within the tumor infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted but activated (Tex/act) subpopulations critical to the improvement of therapeutic approaches. To investigate mechanisms associated with Tex/act cells, we sorted and performed transcriptional profiling of CD8+ tumor infiltrating lymphocytes (TIL) coexpressing the exhaustion markers PD-1 and TIM-3, from large volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single cell level, to identify potential mechanisms that underlie their dysfunctional phenotype. We identified novel dysregulated pathways in CD8+PD-1+TIM-3+ cells that have not been well studied in TIL; these include bile acid and peroxisome pathway-related metabolism, and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression. Through bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma.

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“…0.085µM 25-HC signi cantly triggered the expression of ERβ. ERβ knockdown blocked the effect of 25-HC on LAC proliferation, migration and invasion.27hydroxycholesterol, as a structural analogue of 25-HC, has been identi ed as an ERβ-selective regulator (SERM) that dose-dependently inhibited ERβ transcriptional activity in aortic endothelial cells and breast cancer cells [19], but dose-dependently elevated ERβ transcriptional activity in hepatocellular carcinoma cells and colon cancer cells [20]. These ndings suggest that the actions of 27-hydroxycholesterol are cell-type speci c. However, the role of ERβ in 25-HC-mediated actions remained largely unknown.…”

Section: Relationship Between the Expression Of Erβ And Tnfrsf17 And ...mentioning

confidence: 99%

25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERβ/TNFRSF17 axis

Lin

He²,

Jiang³

et al. 2023

Preprint

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Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERβ) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERβ expression in LAC. Knockdown of ERβ inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERβ knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERβ knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERβ and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERβ/TNFRSF17 axis.

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The emerging role of 27-hydroxycholesterol in cancer development and progression: An update

Cited by 26 publications

References 219 publications

The role of lipid metabolic reprogramming in tumor microenvironment

The role of lipid metabolic reprogramming in tumor microenvironment

Re-evaluating the melanoma TIL compartment and its unexpected spectrum of exhausted and functional T cells

25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERβ/TNFRSF17 axis

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