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Dissecting phenotypic responses of the druggable targetome in cancersopen access

Authors
Jeong, EunaPark, ChoaMoon, Sung UngCho, JuyeonSong, MeeRyoo, SeungeunGu, HyejeongLee, YejinKim, WooyoungYoon, Sukjoon
Issue Date
Aug-2019
Publisher
NATURE PUBLISHING GROUP
Citation
SCIENTIFIC REPORTS, v.9
Journal Title
SCIENTIFIC REPORTS
Volume
9
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/2921
DOI
10.1038/s41598-019-48989-2
ISSN
2045-2322
Abstract
Although a large amount of screening data comprising target genes and/or drugs tested against cancer cell line panels are available, different assay conditions and readouts limit the integrated analysis and batch-to-batch comparison of these data. Here, we systematically produced and analyzed the anticancer effect of the druggable targetome to understand the varied phenotypic outcomes of diverse functional classes of target genes. A library of siRNAs targeting similar to 4,800 druggable genes was screened against cancer cell lines under 2D and/or 3D assay conditions. The anticancer effect was simultaneously measured by quantifying cell proliferation and/or viability. Hit rates varied significantly depending on assay conditions and/or phenotypic readouts. Functional classes of hit genes were correlated with the microenvironment difference between the 2D monolayer cell proliferation and 3D sphere formation assays. Furthermore, multiplexing of cell proliferation and viability measures enabled us to compare the sensitivity and resistance responses to the gene knockdown. Many target genes that inhibited cell proliferation increased the single-cell-level viability of surviving cells, leading to an increase in self-renewal potential. In this study, combinations of parallel 2D/3D assays and multiplexing of cell proliferation and viability measures provided functional insights into the varied phenotypic outcomes of the cancer targetome.
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