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FABP4 as a key determinant of metastatic potential of ovarian cancer

The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastat...

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Autores principales: Gharpure, Kshipra M., Pradeep, Sunila, Sans, Marta, Rupaimoole, Rajesha, Ivan, Cristina, Wu, Sherry Y., Bayraktar, Emine, Nagaraja, Archana S., Mangala, Lingegowda S., Zhang, Xinna, Haemmerle, Monika, Hu, Wei, Rodriguez-Aguayo, Cristian, McGuire, Michael, Mak, Celia Sze Ling, Chen, Xiuhui, Tran, Michelle A., Villar-Prados, Alejandro, Pena, Guillermo Armaiz, Kondetimmanahalli, Ragini, Nini, Ryan, Koppula, Pranavi, Ram, Prahlad, Liu, Jinsong, Lopez-Berestein, Gabriel, Baggerly, Keith, S. Eberlin, Livia, Sood, Anil K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062524/
https://www.ncbi.nlm.nih.gov/pubmed/30050129
http://dx.doi.org/10.1038/s41467-018-04987-y
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author Gharpure, Kshipra M.
Pradeep, Sunila
Sans, Marta
Rupaimoole, Rajesha
Ivan, Cristina
Wu, Sherry Y.
Bayraktar, Emine
Nagaraja, Archana S.
Mangala, Lingegowda S.
Zhang, Xinna
Haemmerle, Monika
Hu, Wei
Rodriguez-Aguayo, Cristian
McGuire, Michael
Mak, Celia Sze Ling
Chen, Xiuhui
Tran, Michelle A.
Villar-Prados, Alejandro
Pena, Guillermo Armaiz
Kondetimmanahalli, Ragini
Nini, Ryan
Koppula, Pranavi
Ram, Prahlad
Liu, Jinsong
Lopez-Berestein, Gabriel
Baggerly, Keith
S. Eberlin, Livia
Sood, Anil K.
author_facet Gharpure, Kshipra M.
Pradeep, Sunila
Sans, Marta
Rupaimoole, Rajesha
Ivan, Cristina
Wu, Sherry Y.
Bayraktar, Emine
Nagaraja, Archana S.
Mangala, Lingegowda S.
Zhang, Xinna
Haemmerle, Monika
Hu, Wei
Rodriguez-Aguayo, Cristian
McGuire, Michael
Mak, Celia Sze Ling
Chen, Xiuhui
Tran, Michelle A.
Villar-Prados, Alejandro
Pena, Guillermo Armaiz
Kondetimmanahalli, Ragini
Nini, Ryan
Koppula, Pranavi
Ram, Prahlad
Liu, Jinsong
Lopez-Berestein, Gabriel
Baggerly, Keith
S. Eberlin, Livia
Sood, Anil K.
author_sort Gharpure, Kshipra M.
collection PubMed
description The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels. Treatment with DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA inhibited tumor progression in mouse models. With RPPA and metabolite arrays, we found that FABP4 regulates pathways associated with metastasis and affects metabolic pathways in ovarian cancer cells. Collectively, these findings demonstrate that FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer.
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spelling pubmed-60625242018-07-30 FABP4 as a key determinant of metastatic potential of ovarian cancer Gharpure, Kshipra M. Pradeep, Sunila Sans, Marta Rupaimoole, Rajesha Ivan, Cristina Wu, Sherry Y. Bayraktar, Emine Nagaraja, Archana S. Mangala, Lingegowda S. Zhang, Xinna Haemmerle, Monika Hu, Wei Rodriguez-Aguayo, Cristian McGuire, Michael Mak, Celia Sze Ling Chen, Xiuhui Tran, Michelle A. Villar-Prados, Alejandro Pena, Guillermo Armaiz Kondetimmanahalli, Ragini Nini, Ryan Koppula, Pranavi Ram, Prahlad Liu, Jinsong Lopez-Berestein, Gabriel Baggerly, Keith S. Eberlin, Livia Sood, Anil K. Nat Commun Article The standard treatment for high-grade serous ovarian cancer is primary debulking surgery followed by chemotherapy. The extent of metastasis and invasive potential of lesions can influence the outcome of these primary surgeries. Here, we explored the underlying mechanisms that could increase metastatic potential in ovarian cancer. We discovered that FABP4 (fatty acid binding protein) can substantially increase the metastatic potential of cancer cells. We also found that miR-409-3p regulates FABP4 in ovarian cancer cells and that hypoxia decreases miR-409-3p levels. Treatment with DOPC nanoliposomes containing either miR-409-3p mimic or FABP4 siRNA inhibited tumor progression in mouse models. With RPPA and metabolite arrays, we found that FABP4 regulates pathways associated with metastasis and affects metabolic pathways in ovarian cancer cells. Collectively, these findings demonstrate that FABP4 is functionally responsible for aggressive patterns of disease that likely contribute to poor prognosis in ovarian cancer. Nature Publishing Group UK 2018-07-26 /pmc/articles/PMC6062524/ /pubmed/30050129 http://dx.doi.org/10.1038/s41467-018-04987-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gharpure, Kshipra M.
Pradeep, Sunila
Sans, Marta
Rupaimoole, Rajesha
Ivan, Cristina
Wu, Sherry Y.
Bayraktar, Emine
Nagaraja, Archana S.
Mangala, Lingegowda S.
Zhang, Xinna
Haemmerle, Monika
Hu, Wei
Rodriguez-Aguayo, Cristian
McGuire, Michael
Mak, Celia Sze Ling
Chen, Xiuhui
Tran, Michelle A.
Villar-Prados, Alejandro
Pena, Guillermo Armaiz
Kondetimmanahalli, Ragini
Nini, Ryan
Koppula, Pranavi
Ram, Prahlad
Liu, Jinsong
Lopez-Berestein, Gabriel
Baggerly, Keith
S. Eberlin, Livia
Sood, Anil K.
FABP4 as a key determinant of metastatic potential of ovarian cancer
title FABP4 as a key determinant of metastatic potential of ovarian cancer
title_full FABP4 as a key determinant of metastatic potential of ovarian cancer
title_fullStr FABP4 as a key determinant of metastatic potential of ovarian cancer
title_full_unstemmed FABP4 as a key determinant of metastatic potential of ovarian cancer
title_short FABP4 as a key determinant of metastatic potential of ovarian cancer
title_sort fabp4 as a key determinant of metastatic potential of ovarian cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062524/
https://www.ncbi.nlm.nih.gov/pubmed/30050129
http://dx.doi.org/10.1038/s41467-018-04987-y
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