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Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration

BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show tha...

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Autores principales: Balaban, Seher, Shearer, Robert F., Lee, Lisa S., van Geldermalsen, Michelle, Schreuder, Mark, Shtein, Harrison C., Cairns, Rose, Thomas, Kristen C., Fazakerley, Daniel J., Grewal, Thomas, Holst, Jeff, Saunders, Darren N., Hoy, Andrew J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237166/
https://www.ncbi.nlm.nih.gov/pubmed/28101337
http://dx.doi.org/10.1186/s40170-016-0163-7
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author Balaban, Seher
Shearer, Robert F.
Lee, Lisa S.
van Geldermalsen, Michelle
Schreuder, Mark
Shtein, Harrison C.
Cairns, Rose
Thomas, Kristen C.
Fazakerley, Daniel J.
Grewal, Thomas
Holst, Jeff
Saunders, Darren N.
Hoy, Andrew J.
author_facet Balaban, Seher
Shearer, Robert F.
Lee, Lisa S.
van Geldermalsen, Michelle
Schreuder, Mark
Shtein, Harrison C.
Cairns, Rose
Thomas, Kristen C.
Fazakerley, Daniel J.
Grewal, Thomas
Holst, Jeff
Saunders, Darren N.
Hoy, Andrew J.
author_sort Balaban, Seher
collection PubMed
description BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from “obese” adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40170-016-0163-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-52371662017-01-18 Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration Balaban, Seher Shearer, Robert F. Lee, Lisa S. van Geldermalsen, Michelle Schreuder, Mark Shtein, Harrison C. Cairns, Rose Thomas, Kristen C. Fazakerley, Daniel J. Grewal, Thomas Holst, Jeff Saunders, Darren N. Hoy, Andrew J. Cancer Metab Research BACKGROUND: Obesity is associated with increased recurrence and reduced survival of breast cancer. Adipocytes constitute a significant component of breast tissue, yet their role in provisioning metabolic substrates to support breast cancer progression is poorly understood. RESULTS: Here, we show that co-culture of breast cancer cells with adipocytes revealed cancer cell-stimulated depletion of adipocyte triacylglycerol. Adipocyte-derived free fatty acids were transferred to breast cancer cells, driving fatty acid metabolism via increased CPT1A and electron transport chain complex protein levels, resulting in increased proliferation and migration. Notably, fatty acid transfer to breast cancer cells was enhanced from “obese” adipocytes, concomitant with increased stimulation of cancer cell proliferation and migration. This adipocyte-stimulated breast cancer cell proliferation was dependent on lipolytic processes since HSL/ATGL knockdown attenuated cancer cell responses. CONCLUSIONS: These findings highlight a novel and potentially important role for adipocyte lipolysis in the provision of metabolic substrates to breast cancer cells, thereby supporting cancer progression. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40170-016-0163-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-01-13 /pmc/articles/PMC5237166/ /pubmed/28101337 http://dx.doi.org/10.1186/s40170-016-0163-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Balaban, Seher
Shearer, Robert F.
Lee, Lisa S.
van Geldermalsen, Michelle
Schreuder, Mark
Shtein, Harrison C.
Cairns, Rose
Thomas, Kristen C.
Fazakerley, Daniel J.
Grewal, Thomas
Holst, Jeff
Saunders, Darren N.
Hoy, Andrew J.
Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title_full Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title_fullStr Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title_full_unstemmed Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title_short Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
title_sort adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237166/
https://www.ncbi.nlm.nih.gov/pubmed/28101337
http://dx.doi.org/10.1186/s40170-016-0163-7
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