Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.
Antineoplastic Agents
/ pharmacology
Cell Line, Tumor
Cell Shape
Clone Cells
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Library
Genes, Neoplasm
Hedgehog Proteins
/ genetics
Humans
Inhibitory Concentration 50
Kaplan-Meier Estimate
Ovarian Neoplasms
/ genetics
Phenotype
Prognosis
RNA, Messenger
/ genetics
RNA, Neoplasm
/ genetics
RNA, Small Interfering
/ genetics
Side-Population Cells
/ chemistry
Signal Transduction
Spheroids, Cellular
Transfection
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
02 10 2019
02 10 2019
Historique:
received:
05
04
2019
accepted:
19
09
2019
entrez:
4
10
2019
pubmed:
4
10
2019
medline:
11
11
2020
Statut:
epublish
Résumé
Side population (SP) cells harbor malignant phenotypes in cancer. The aim of this study was to identify genes that modulate the proportion of ovarian cancer SP cells. Using a shRNA library targeting 15,000 genes, a functional genomics screen was performed to identify genes whose suppression increased the SP percentage. The biological effects caused by alteration of those identified genes were investigated in vitro and in vivo. We found that suppression of MSL3, ZNF691, VPS45, ITGB3BP, TLE2, and ZNF498 increased the proportion of SP cells. Newly generated SP cells exhibit greater capacity for sphere formation, single cell clonogenicity, and in vivo tumorigenicity. On the contrary, overexpression of MSL3, VPS45, ITGB3BP, TLE2, and ZNF498 decreased the proportion of SP cells, sphere formation capacity and single cell clonogenicity. In ovarian cancer cases, low expression of MSL3, ZNF691 and VPS45 was related to poor prognosis. Suppression of these six genes enhanced activity of the hedgehog pathway. Cyclopamine, a hedgehog pathway inhibitor, significantly decreased the number of SP cells and their sphere forming ability. Our results provide new information regarding molecular mechanisms favoring SP cells and suggest that Hedgehog signaling may provide a viable target for ovarian cancer.
Identifiants
pubmed: 31578411
doi: 10.1038/s41598-019-50794-w
pii: 10.1038/s41598-019-50794-w
pmc: PMC6775117
doi:
Substances chimiques
Antineoplastic Agents
0
Hedgehog Proteins
0
RNA, Messenger
0
RNA, Neoplasm
0
RNA, Small Interfering
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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