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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Published in:Nature communications Vol. 9; no. 1; pp. 2923 - 14
Main Authors: 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.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 26.07.2018
Nature Publishing Group
Nature Portfolio
Subjects:
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13/51
38/109
38/32
38/77
631/67/1059
631/67/1517/1709
631/67/322
Animal models
Animals
Cancer
Cell Line, Tumor
Chemotherapy
Fatty acid-binding protein
Fatty Acid-Binding Proteins - genetics
Fatty Acid-Binding Proteins - metabolism
Female
Gene Expression Regulation, Neoplastic - genetics
Gene Expression Regulation, Neoplastic - physiology
Humanities and Social Sciences
Humans
Hypoxia
Invasiveness
Lesions
Metabolic pathways
Metabolites
Metastases
Metastasis
Mice
Mice, Nude
MicroRNAs - genetics
MicroRNAs - metabolism
multidisciplinary
Neoplasm Invasiveness - genetics
Neoplasm Invasiveness - pathology
Ovarian cancer
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Proteins
Science
Science (multidisciplinary)
siRNA
Surgery
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. In ovarian cancer, metastatic phenotype may impact surgical outcomes. Here, the authors show miR-409-3p regulates FABP4 which can increase metastatic potential of ovarian cancer, and treatment with DOPC nanoliposomes containing either miR-409--3p mimic or FABP4 siRNA inhibits tumor progression in mice.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-018-04987-y