期刊
ISCIENCE
卷 19, 期 -, 页码 474-+出版社
CELL PRESS
DOI: 10.1016/j.isci.2019.07.049
关键词
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资金
- National Institutes of Health [R00CA194318, R01CA117907, R01GM120109]
- Department of Defense OCRP [OC170228]
- American Cancer Society [16-184-56]
- University of Colorado Department of Obstetrics and Gynecology Academic Enrichment Fund (AEF)
- RNA Biosciences Initiative
- University of Colorado Cancer Center Support Grant [P30CA046934]
High-grade serous ovarian cancers (HGSOCs) arise from exfoliation of transformed cells from the fallopian tube, indicating that survival in suspension, and potentially escape from anoikis, is required for dissemination. We report here the results of a multi-omic study to identify drivers of anoikis escape, including transcriptomic analysis, global non-targeted metabolomics, and a genome-wide CRISPR/Cas9 knockout (GeCKO) screen of HGSOC cells cultured in adherent and suspension settings. Our combined approach identified known pathways, including NOTCH signaling, as well as novel regulators of anoikis escape. Newly identified genes include effectors of fatty acid metabolism, ACADVL and ECHDC2, and an autophagy regulator, ULK1. Knockdown of these genes significantly inhibited suspension growth of HGSOC cells, and the metabolic profile confirmed the role of fatty acid metabolism in survival in suspension. Integration of our datasets identified an anoikis-escape gene signature that predicts overall survival in many carcinomas.
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