FABP4 as a key determinant of metastatic potential of ovarian cancer

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作者
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
机构
[1] The University of Texas MD Anderson Cancer Center,Department of Gynecologic Oncology and Reproductive Medicine
[2] Medical College of Wisconsin,Department of Obstetrics and Gynecology
[3] The University of Texas at Austin,Department of Chemistry
[4] Harvard Medical School,Department of Pathology and Institute of RNA Medicine, Beth Israel Deaconess Medical Center Cancer Center
[5] The University of Texas MD Anderson Cancer Center,Center for RNA Interference and Non
[6] The University of Texas MD Anderson Cancer Center,Coding RNA
[7] Institute of Pathology,Department of Experimental Therapeutics
[8] Ponce Health Sciences University,Martin
[9] The University of Texas at Austin,Luther
[10] The University of Texas MD Anderson Cancer Center,University Halle
[11] The University of Texas MD Anderson Cancer Center,Wittenberg
[12] The University of Texas MD Anderson Cancer Center,Department of Pharmacology
[13] The University of Texas MD Anderson Cancer Center,Graduate School of Biomedical Sciences
[14] The University of Texas MD Anderson Cancer Center,Department of Experimental Radiation Oncology
[15] The University of Texas MD Anderson Cancer Center,Department of Systems Biology
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摘要
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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