Journal
FASEB JOURNAL
Volume 31, Issue 2, Pages 625-635Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201600953
Keywords
CSLC sphere culture; lipid profile; network analysis; siRNA screening
Categories
Funding
- National Research Foundation (NRF) of Korea - Korean government (MEST) [NRF-2012M3A9B6055398, NRF-2012M3A9B6055466, NRF-2016R1A5A1011974, NRF-2013R1A1A2059115, NRF-2015R1D1A1A01056594]
- National Research Foundation of Korea [2012M3A9B6055398, 2012M3A9B6055466] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Cancer stem-like cells (CSLCs) contribute to the initiation and recurrence of tumors and to their resistance to conventional therapies. In this study, small interfering RNA (siRNA)-based screening of approximate to 4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk-cultured population only, or both populations. While diverse biologic processes were associated with siRNAs reducing the bulk-cultured population, CSLC-eliminating siRNAs were enriched in a few functional categories, such as lipid metabolism, protein metabolism, and gene expression. Interestingly, siRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. The lipidomic profile of CSLCs revealed increased levels of monounsaturated lipids. Pharmacologic blockage of these target pathways reduced CSLCs, and this effect was eliminated by addition of downstream metabolite products. The present CSLC-sensitive target categories provide a useful resource that can be exploited for the selective elimination of CSLCs.
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