Obesity and Cancer: 27-Hydroxycholesterol, the Missing Link

Asghari, Arvand; Umetani, Michihisa

doi:10.3390/ijms21144822

Cited by 29 publications

(25 citation statements)

References 101 publications

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“…Some studies highlight the link among lipid metabolism, growth, and metastasis in breast cancer. For example, a recent report illustrated that 27-hydroxy cholesterol is synthesized from cholesterol within cancer cells and increases breast cancer growth and metastasis, binding to estrogen receptor alpha and activating oncogenic estrogen signaling [ 34 ]. The expression of cytochrome P450 CYP27A1, which converts cholesterol to 27-hydroxy cholesterol, is high in epithelial breast tumors, and its expression is positively associated with the tumor grade [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Rizzo¹,

Colombo²,

Montorfano³

et al. 2021

Cells

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(1) Background: Lipid metabolism is a fundamental hallmark of all tumors, especially of breast cancer. Few studies describe the different lipid metabolisms and sensitivities to the microenvironment of breast cancer cell subtypes that influence the proliferation, aggressiveness, and success of therapy. This study describes the impact of lipid microenvironment on endoplasmic reticulum (ER) membrane and metabolic activity in two breast cancer cell lines with Luminal A and triple-negative breast cancer (TNBC) features. (2) Methods: We investigated the peculiar lipid phenotype of a TNBC cell line, MDA-MB-231, and a Luminal A cell line, MCF7, and their different sensitivity to exogenous fatty acids (i.e., palmitic acid (PA) and docosahexaenoic acid (DHA)). Moreover, we verified the impact of exogenous fatty acids on ER lipid composition. (3) Results: The data obtained demonstrate that MDA-MB-231 cells are more sensitive to the lipid microenvironment and that both PA and DHA are able to remodel their ER membranes with consequences on resident enzyme activity. On the contrary, MCF7 cells are less sensitive to PA, whereas they incorporate DHA, although less efficiently than MDA-MB-231 cells. (4) Conclusions: This study sustains the importance of lipid metabolism as an innovative hallmark to discriminate breast cancer subclasses and to develop personalized and innovative pharmacological strategies. The different sensitivities to the lipid environment shown by MCF7 and MDA-MB-231 cells might be related to cell malignancy and chemoresistance onset. In the future, this new approach could lead to a substantial decrease both in deleterious side effects for the patients and in the cost of entire therapeutic treatments coupled with increased therapy efficiency.

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Section: Discussionmentioning

confidence: 99%

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Rizzo¹,

Colombo²,

Montorfano³

et al. 2021

Cells

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“…In a recent evaluation of a cohort from the European Investigation into Cancer and Nutrition (EPIC) study, no association between circulating 27-HC levels and premenopausal breast cancer risk was found, and an inverse correlation was reported in postmenopausal women (222,223). These results suggest that the estrogen levels may influence the association between 27-HC and breast cancer risk and survival (224).…”

Section: Mechanisms Underlying the Obesity-cancer Relationship: The Contribution Of Lipids Cholesterol Uptakementioning

confidence: 96%

Obesity, Type 2 Diabetes, and Cancer Risk

2021

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Obesity and type 2 diabetes have both been associated with increased cancer risk and are becoming increasingly prevalent. Metabolic abnormalities such as insulin resistance and dyslipidemia are associated with both obesity and type 2 diabetes and have been implicated in the obesity-cancer relationship. Multiple mechanisms have been proposed to link obesity and diabetes with cancer progression, including an increase in insulin/IGF-1 signaling, lipid and glucose uptake and metabolism, alterations in the profile of cytokines, chemokines, and adipokines, as well as changes in the adipose tissue directly adjacent to the cancer sites. This review aims to summarize and provide an update on the epidemiological and mechanistic evidence linking obesity and type 2 diabetes with cancer, focusing on the roles of insulin, lipids, and adipose tissue.

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Section: Adipose-derived Pathophysiological Mechanisms Linking Ec mentioning

confidence: 99%

“…As a cholesterol metabolite, 27-hydroxycholesterol (27HC) functions as an endogenous selective ER modulator (SERM). Serum concentrations of ER increase with age and with serum cholesterol levels [40]. Obesity constitutes a risk factor for EC; therefore, adipose tissue must be seen as a highly complex, multifactorial component in tumorigenesis.…”

Section: Adipose Tissue-an Endocrine Organmentioning

confidence: 99%

Obesity Epidemic—The Underestimated Risk of Endometrial Cancer

Kiesel

Eichbaum

Baumeier

et al. 2020

Cancers

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Endometrial cancer (EC) is the most frequently observed malignant gynecologic disease in developed countries. There is a strong association between the established risk factor obesity and the incidence of EC. Furthermore, the rate of women with a body mass index (BMI) > 30 kg/m2 is increasing worldwide, correspondingly leading to a higher prevalence of EC. Understanding the adipose tissue as an endocrine organ, elementary pathophysiological pathways of tumorigenesis have been revealed. This includes the fundamental role of hyperglycemia, insulin resistance, and hyperestrogenemia, as well as interactions with a chronic proinflammatory microenvironment. Therapeutic options potentially include metformin or bariatric surgery. Moreover, changes in individual lifestyle such as weight reduction, physical activity, and an awareness of healthy nutrition are effective in preventing the disease.

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Obesity and Cancer: 27-Hydroxycholesterol, the Missing Link

Cited by 29 publications

References 101 publications

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Exogenous Fatty Acids Modulate ER Lipid Composition and Metabolism in Breast Cancer Cells

Obesity, Type 2 Diabetes, and Cancer Risk

Obesity Epidemic—The Underestimated Risk of Endometrial Cancer

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