FABP4 as a key determinant of metastatic potential of ovarian cancer

Kshipra M. Gharpure(The University of Texas MD Anderson Cancer Center), Sunila Pradeep(The University of Texas MD Anderson Cancer Center), Marta Sans(The University of Texas at Austin), Rajesha Rupaimoole(Beth Israel Deaconess Medical Center), Cristina Ivan(The University of Texas MD Anderson Cancer Center), Sherry Y. Wu(The University of Texas MD Anderson Cancer Center), Emine Bayraktar(The University of Texas MD Anderson Cancer Center), Archana S. Nagaraja(The University of Texas MD Anderson Cancer Center), Lingegowda S. Mangala(The University of Texas MD Anderson Cancer Center), Xinna Zhang(The University of Texas MD Anderson Cancer Center), Monika Haemmerle(Martin Luther University Halle-Wittenberg), Wei Hu(The University of Texas MD Anderson Cancer Center), Cristian Rodriguez‐Aguayo(The University of Texas MD Anderson Cancer Center), Michael H. McGuire(The University of Texas MD Anderson Cancer Center), Celia Sze Ling Mak(The University of Texas MD Anderson Cancer Center), Xiuhui Chen(The University of Texas MD Anderson Cancer Center), Michelle Tran(The University of Texas MD Anderson Cancer Center), Alejandro Villar‐Prados(The University of Texas MD Anderson Cancer Center), Guillermo N. Armaiz-Peña(Ponce Health Sciences University), Ragini Kondetimmanahalli(The University of Texas at Austin), Ryan Nini(The University of Texas MD Anderson Cancer Center), Pranavi Koppula(The University of Texas MD Anderson Cancer Center), Prahlad T. Ram(The University of Texas MD Anderson Cancer Center), Jinsong Liu(The University of Texas MD Anderson Cancer Center), Gabriel Lopez‐Berestein(The University of Texas MD Anderson Cancer Center), Keith Baggerly(The University of Texas MD Anderson Cancer Center), Lívia S. Eberlin(The University of Texas at Austin), Anil K. Sood(The University of Texas MD Anderson Cancer Center)
Nature Communications
July 20, 2018
10.1038/s41467-018-04987-y
Cited by 215Open Access
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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.

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