FABP4 as a key determinant of metastatic potential of ovarian cancer

Kshipra M. Gharpure; Sunila Pradeep; Marta Sans; Rajesha Rupaimoole; Cristina Ivan; Sherry Y. Wu; Emine Bayraktar; Archana S. Nagaraja; Lingegowda S. Mangala; Xinna Zhang; Monika Haemmerle; Wei Hu; Cristian Rodriguez-Aguayo; Michael McGuire; Celia Sze Ling Mak; Xiuhui Chen; Michelle A. Tran; Alejandro Villar-Prados; Guillermo Armaiz Pena; Ragini Kondetimmanahalli; Ryan Nini; Pranavi Koppula; Prahlad Ram; Jinsong Liu; Gabriel Lopez-Berestein; Keith Baggerly; Livia S. Eberlin; Anil K. Sood

doi:10.1038/s41467-018-04987-y

FABP4 as a key determinant of metastatic potential of ovarian cancer

Kshipra M. Gharpure, Sunila Pradeep, Marta Sans, Rajesha Rupaimoole, Cristina Ivan, Sherry Y. Wu, Emine Bayraktar, Archana S. Nagaraja, Lingegowda S. Mangala, Xinna Zhang, Monika Haemmerle, Wei Hu, Cristian Rodriguez-Aguayo, Michael McGuire, Celia Sze Ling Mak, Xiuhui Chen, Michelle A. Tran, Alejandro Villar-Prados, Guillermo Armaiz Pena, Ragini KondetimmanahalliRyan Nini, Pranavi Koppula, Prahlad Ram, Jinsong Liu, Gabriel Lopez-Berestein, Keith Baggerly, Livia S. Eberlin, Anil K. Sood

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Abstract

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.

Original language	English (US)
Article number	2923
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04987-y
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Gharpure, K. M., Pradeep, S., Sans, M., Rupaimoole, R., Ivan, C., Wu, S. Y., Bayraktar, E., Nagaraja, A. S., Mangala, L. S., Zhang, X., Haemmerle, M., Hu, W., Rodriguez-Aguayo, C., McGuire, M., Mak, C. S. L., Chen, X., Tran, M. A., Villar-Prados, A., Pena, G. A., ... Sood, A. K. (2018). FABP4 as a key determinant of metastatic potential of ovarian cancer. Nature communications, 9(1), Article 2923. https://doi.org/10.1038/s41467-018-04987-y

Gharpure, KM, Pradeep, S, Sans, M, Rupaimoole, R, Ivan, C, Wu, SY, Bayraktar, E, Nagaraja, AS, Mangala, LS, Zhang, X, Haemmerle, M, Hu, W , Rodriguez-Aguayo, C, McGuire, M, Mak, CSL, Chen, X, Tran, MA, Villar-Prados, A, Pena, GA, Kondetimmanahalli, R, Nini, R, Koppula, P, Ram, P, Liu, J , Lopez-Berestein, G, Baggerly, K, S. Eberlin, L & Sood, AK 2018, 'FABP4 as a key determinant of metastatic potential of ovarian cancer', Nature communications, vol. 9, no. 1, 2923. https://doi.org/10.1038/s41467-018-04987-y

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title = "FABP4 as a key determinant of metastatic potential of ovarian cancer",

abstract = "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.",

author = "Gharpure, {Kshipra M.} and Sunila Pradeep and Marta Sans and Rajesha Rupaimoole and Cristina Ivan and Wu, {Sherry Y.} and Emine Bayraktar and Nagaraja, {Archana S.} and Mangala, {Lingegowda S.} and Xinna Zhang and Monika Haemmerle and Wei Hu and Cristian Rodriguez-Aguayo and Michael McGuire and Mak, {Celia Sze Ling} and Xiuhui Chen and Tran, {Michelle A.} and Alejandro Villar-Prados and Pena, {Guillermo Armaiz} and Ragini Kondetimmanahalli and Ryan Nini and Pranavi Koppula and Prahlad Ram and Jinsong Liu and Gabriel Lopez-Berestein and Keith Baggerly and {S. Eberlin}, Livia and Sood, {Anil K.}",

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doi = "10.1038/s41467-018-04987-y",

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AU - Gharpure, Kshipra M.

AU - Pradeep, Sunila

AU - Sans, Marta

AU - Rupaimoole, Rajesha

AU - Ivan, Cristina

AU - Wu, Sherry Y.

AU - Bayraktar, Emine

AU - Nagaraja, Archana S.

AU - Mangala, Lingegowda S.

AU - Zhang, Xinna

AU - Haemmerle, Monika

AU - Hu, Wei

AU - Rodriguez-Aguayo, Cristian

AU - McGuire, Michael

AU - Mak, Celia Sze Ling

AU - Chen, Xiuhui

AU - Tran, Michelle A.

AU - Villar-Prados, Alejandro

AU - Pena, Guillermo Armaiz

AU - Kondetimmanahalli, Ragini

AU - Nini, Ryan

AU - Koppula, Pranavi

AU - Ram, Prahlad

AU - Liu, Jinsong

AU - Lopez-Berestein, Gabriel

AU - Baggerly, Keith

AU - S. Eberlin, Livia

AU - Sood, Anil K.

PY - 2018/12/1

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N2 - 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.

AB - 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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FABP4 as a key determinant of metastatic potential of ovarian cancer

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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