HER2 (erbB-2)-targeted effects of the ϖ-3 polyunsaturated. Fatty acid α-linolenic acid (ALA; 18:3n-3) in breast cancer cells: the «fat features» of the «Mediterranean diet» as an «anti-HER2 cocktail»

2006 ◽  
Vol 8 (11) ◽  
pp. 812-820 ◽  
Author(s):  
Javier A. Menéndez ◽  
Alejandro Vázquez-Martín ◽  
Santiago Ropero ◽  
Ramón Colomer ◽  
Ruth Lupu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Linolenic Acid ◽  
Mediterranean Diet ◽  
Polyunsaturated Fatty Acid ◽  
Breast Cancer Cells ◽  
The Mediterranean

scholarly journals Estrogen Enhances the Expression of the Polyunsaturated Fatty Acid Elongase Elovl2 via ERα in Breast Cancer Cells

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164241 ◽  
Author(s):  
Amanda González-Bengtsson ◽  
Abolfazl Asadi ◽  
Hui Gao ◽  
Karin Dahlman-Wright ◽  
Anders Jacobsson
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Polyunsaturated Fatty Acid ◽  
Breast Cancer Cells ◽  
Fatty Acid Elongase

scholarly journals α-Linolenic Acid Induces Breast Cancer Cell Apoptosis by Down-Regulating Human Fatty Acid Synthase

2021 ◽  
Author(s):  
Wenyuan Huang ◽  
Xing Guo ◽  
Huijin Fan ◽  
Amantay Alzhan ◽  
Zhengan Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Linolenic Acid ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Fatty Acid Synthase ◽  
Human Breast Cancer Cells ◽  
Human Breast

Abstract Background/Aims: Fatty acid synthase (FASN) is a multi-enzyme complex that synthesizes endogenous fatty acids. The overexpression of FASN has been reported in variety of cancers, including breast, ovarian, prostrate, and colon cancers, which strongly indicates the involvement of FASN in cancer progression. α-Linolenic acid (ALA) has many biological activities, including anti-cancer effects. The aim of the present study was to investigate the inhibitory effect of ALA on fatty acid synthesis pathway and apoptosis of human breast cancer cells. Methods: Cytotoxicity of ALA in human breast cancer cells (MDA-MB-231 and MCF-7 cells) was assessed by MTT assay. Changes in protein expression were detected by immunoblot analysis. Cell migration was detected by wound healing and cell transwell assay. Apoptotic effects, mitochondrial membrane potential and cell cycle analysis were detected by flow cytometry. Molecular docking was carried out with the AutoDockTools program suite to analyze the binding abilities of ALA on thioesterase (TE) domain of FASN. Results: We found that the expression levels of FASN decreased significantly in ALA treated breast cancer cells. Compared with palmitic acid (PA), ALA reduced cell viability in a dose-dependent manner. ALA showed a higher affinity with the TE domain than PA. ALA induced breast cancer cells apoptosis, which effects were similar with the knockdown of FASN. In addition, ALA inhibited the invasion and metastasis, and arrested cell cycle in breast cancer cells. Conclusion: We propose a hypothesis that ALA could contribute to the treatment of human breast cancer by inhibiting FASN.

scholarly journals Fatty Acid Synthase Confers Tamoxifen Resistance to ER+/HER2+ Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1132
Author(s):  
Javier A. Menendez ◽  
Adriana Papadimitropoulou ◽  
Travis Vander Steen ◽  
Elisabet Cuyàs ◽  
Bharvi P. Oza-Gajera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Promoter Activity ◽  
Fatty Acid Synthase ◽  
Endocrine Resistance ◽  
Gene Promoter ◽  
Her2 Positive ◽  
Her2 Breast Cancer

The identification of clinically important molecular mechanisms driving endocrine resistance is a priority in estrogen receptor-positive (ER+) breast cancer. Although both genomic and non-genomic cross-talk between the ER and growth factor receptors such as human epidermal growth factor receptor 2 (HER2) has frequently been associated with both experimental and clinical endocrine therapy resistance, combined targeting of ER and HER2 has failed to improve overall survival in endocrine non-responsive disease. Herein, we questioned the role of fatty acid synthase (FASN), a lipogenic enzyme linked to HER2-driven breast cancer aggressiveness, in the development and maintenance of hormone-independent growth and resistance to anti-estrogens in ER/HER2-positive (ER+/HER2+) breast cancer. The stimulatory effects of estradiol on FASN gene promoter activity and protein expression were blunted by anti-estrogens in endocrine-responsive breast cancer cells. Conversely, an AKT/MAPK-related constitutive hyperactivation of FASN gene promoter activity was unaltered in response to estradiol in non-endocrine responsive ER+/HER2+ breast cancer cells, and could be further enhanced by tamoxifen. Pharmacological blockade with structurally and mechanistically unrelated FASN inhibitors fully impeded the strong stimulatory activity of tamoxifen on the soft-agar colony forming capacity—an in vitro metric of tumorigenicity—of ER+/HER2+ breast cancer cells. In vivo treatment with a FASN inhibitor completely prevented the agonistic tumor-promoting activity of tamoxifen and fully restored its estrogen antagonist properties against ER/HER2-positive xenograft tumors in mice. Functional cancer proteomic data from The Cancer Proteome Atlas (TCPA) revealed that the ER+/HER2+ subtype was the highest FASN protein expressor compared to basal-like, HER2-enriched, and ER+/HER2-negative breast cancer groups. FASN is a biological determinant of HER2-driven endocrine resistance in ER+ breast cancer. Next-generation, clinical-grade FASN inhibitors may be therapeutically relevant to countering resistance to tamoxifen in FASN-overexpressing ER+/HER2+ breast carcinomas.

scholarly journals In Vitro Study of Breast Cancer Cells Exposed to Antisense of Liver Fatty Acid Binding Protein

2006 ◽  
Vol 20 (4) ◽  
Author(s):  
Stacy‐Ann Miller ◽  
Byron Waddy ◽  
Nabarun Chakraborty ◽  
Rasha Hammamieh ◽  
Marti Jett
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Fatty Acid Binding Protein ◽  
In Vitro Study ◽  
Liver Fatty Acid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

scholarly journals Interaction between CD36 and FABP4 modulates adipocyte-induced fatty acid import and metabolism in breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jones Gyamfi ◽  
Joo Hye Yeo ◽  
Doru Kwon ◽  
Byung Soh Min ◽  
Yoon Jin Cha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Mesenchymal Transition ◽  
Genetic Ablation ◽  
Cd36 Expression

AbstractAdipocytes influence breast cancer behaviour via fatty acid release into the tumour microenvironment. Co-culturing human adipocytes and breast cancer cells increased CD36 expression, with fatty acid import into breast cancer cells. Genetic ablation of CD36 attenuates adipocyte-induced epithelial-mesenchymal transition (EMT) and stemness. We show a feedforward loop between CD36 and STAT3; where CD36 activates STAT3 signalling and STAT3 binds to the CD36 promoter, regulating its expression. CD36 expression results in metabolic reprogramming, with a shift towards fatty acid oxidation. CD36 inhibition induces de novo lipogenesis in breast cancer cells. Increased CD36 expression occurs with increased FABP4 expression. We showed that CD36 directly interacts with FABP4 to regulate fatty acid import, transport, and metabolism. CD36 and FABP4 inhibition induces apoptosis in tumour cells. These results indicate that CD36 mediates fatty acid import from adipocytes into cancer cells and activates signalling pathways that drive tumour progression. Targeting CD36 may have a potential for therapy, which will target the tumour microenvironment.

scholarly journals Breast-Associated Adipocytes Secretome Induce Fatty Acid Uptake and Invasiveness in Breast Cancer Cells via CD36 Independently of Body Mass Index, Menopausal Status and Mammary Density

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2012 ◽  
Author(s):  
Maurice Zaoui ◽  
Mehdi Morel ◽  
Nathalie Ferrand ◽  
Soraya Fellahi ◽  
Jean-Philippe Bastard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Body Mass ◽  
Breast Cancer Cells ◽  
Menopausal Status ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Breast Cells

Breast adiposity is correlated with body mass index, menopausal status and mammary density. We here wish to establish how these factors influence the cross-talk between breast adipocytes and normal or malignant breast cells. Adipocyte-derived stem cells (ASCs) were obtained from healthy women and classified into six distinct groups based on body mass index, menopausal status and mammary density. The ASCs were induced to differentiate, and the influence of their conditioned media (ACM) was determined. Unexpectedly, there were no detectable differences in adipogenic differentiation and secretion between the six ASC groups, while their corresponding ACMs had no detectable influence on normal breast cells. In clear contrast, all ACMs profoundly influenced the proliferation, migration and invasiveness of malignant breast cells and increased the number of lipid droplets in their cytoplasm via increased expression of the fatty acid receptor CD36, thereby increasing fatty acid uptake. Importantly, inhibition of CD36 reduced lipid droplet accumulation and attenuated the migration and invasion of the breast cancer cells. These findings suggest that breast-associated adipocytes potentiate the invasiveness of breast cancer cells which, at least in part, is mediated by metabolic reprogramming via CD36-mediated fatty acid uptake.

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