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Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids

Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere‐...

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Autores principales: Luo, Haiqing, Chen, Chih‐Yu, Li, Xiangyong, Zhang, Xin, Su, Chien‐Wen, Liu, Yinghua, Cao, Tinglan, Hao, Lei, Wang, Meng, Kang, Jing X.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292025/
https://www.ncbi.nlm.nih.gov/pubmed/34486791
http://dx.doi.org/10.1002/stem.3452
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author Luo, Haiqing
Chen, Chih‐Yu
Li, Xiangyong
Zhang, Xin
Su, Chien‐Wen
Liu, Yinghua
Cao, Tinglan
Hao, Lei
Wang, Meng
Kang, Jing X.
author_facet Luo, Haiqing
Chen, Chih‐Yu
Li, Xiangyong
Zhang, Xin
Su, Chien‐Wen
Liu, Yinghua
Cao, Tinglan
Hao, Lei
Wang, Meng
Kang, Jing X.
author_sort Luo, Haiqing
collection PubMed
description Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere‐derived MCF‐7 cells and HMLE‐Twist‐ER cells, we found that the cells with stem cell‐like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl‐CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega‐6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self‐renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega‐3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self‐renewal and growth. Dietary supplementation of nude mice bearing BCSC‐derived tumors with omega‐3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self‐renewal and growth of BCSC, and that omega‐3 fatty acids are effective in targeting this pathway to exert their anticancer effect.
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spelling pubmed-92920252022-07-20 Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids Luo, Haiqing Chen, Chih‐Yu Li, Xiangyong Zhang, Xin Su, Chien‐Wen Liu, Yinghua Cao, Tinglan Hao, Lei Wang, Meng Kang, Jing X. Stem Cells Cancer Stem Cells Aberrant lipid metabolism has recently been recognized as a new hallmark of malignancy, but the characteristics of fatty acid metabolism in breast cancer stem cells (BCSC) and potential interventions targeting this pathway remain to be addressed. Here, by using the in vitro BCSC models, mammosphere‐derived MCF‐7 cells and HMLE‐Twist‐ER cells, we found that the cells with stem cell‐like properties exhibited a very distinct profile of fatty acid metabolism compared with that of their parental cancer cells, characterized by increased lipogenesis, especially the activity of stearoyl‐CoA desaturase 1 (SCD1) responsible for the production of monounsaturated fatty acids, and augmented synthesis and utilization of the omega‐6 arachidonic acid (AA). Suppression of SCD1 activity by either enzyme inhibitors or small interfering RNA (siRNA) knockdown strikingly limited self‐renewal and growth of the BCSC, suggesting a key role for SCD1 in BCSC proliferation. Furthermore, elevated levels of SCD1 and other lipogenic enzymes were observed in human breast cancer tissues relative to the noncancer tissues from the same patients and correlated with the pathological grades. Interestingly, treatment of BCSC with omega‐3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, effectively downregulated the expression of the lipogenic enzymes and markedly suppressed BCSC self‐renewal and growth. Dietary supplementation of nude mice bearing BCSC‐derived tumors with omega‐3 fatty acids also significantly reduced their tumor load. These findings have demonstrated that increased lipogenesis is critical for self‐renewal and growth of BCSC, and that omega‐3 fatty acids are effective in targeting this pathway to exert their anticancer effect. John Wiley & Sons, Inc. 2021-09-17 2021-12 /pmc/articles/PMC9292025/ /pubmed/34486791 http://dx.doi.org/10.1002/stem.3452 Text en © 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Cancer Stem Cells
Luo, Haiqing
Chen, Chih‐Yu
Li, Xiangyong
Zhang, Xin
Su, Chien‐Wen
Liu, Yinghua
Cao, Tinglan
Hao, Lei
Wang, Meng
Kang, Jing X.
Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title_full Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title_fullStr Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title_full_unstemmed Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title_short Increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: Impact of omega‐3 fatty acids
title_sort increased lipogenesis is critical for self‐renewal and growth of breast cancer stem cells: impact of omega‐3 fatty acids
topic Cancer Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292025/
https://www.ncbi.nlm.nih.gov/pubmed/34486791
http://dx.doi.org/10.1002/stem.3452
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