Acquisition of a side population fraction augments malignant phenotype in ovarian cancer
Abstract 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...
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Nature Portfolio
2019
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oai:doaj.org-article:44e8b3ffbba9498a88db3b0789ca49982021-12-02T15:08:47ZAcquisition of a side population fraction augments malignant phenotype in ovarian cancer10.1038/s41598-019-50794-w2045-2322https://doaj.org/article/44e8b3ffbba9498a88db3b0789ca49982019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50794-whttps://doaj.org/toc/2045-2322Abstract 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.Koji YamanoiTsukasa BabaKaoru AbikoJunzo HamanishiKen YamaguchiRyusuke MurakamiMana TakiYuko HosoeSusan K. MurphyIkuo KonishiMasaki MandaiNoriomi MatsumuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
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Medicine R Science Q Koji Yamanoi Tsukasa Baba Kaoru Abiko Junzo Hamanishi Ken Yamaguchi Ryusuke Murakami Mana Taki Yuko Hosoe Susan K. Murphy Ikuo Konishi Masaki Mandai Noriomi Matsumura Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| description |
Abstract 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. |
| format |
article |
| author |
Koji Yamanoi Tsukasa Baba Kaoru Abiko Junzo Hamanishi Ken Yamaguchi Ryusuke Murakami Mana Taki Yuko Hosoe Susan K. Murphy Ikuo Konishi Masaki Mandai Noriomi Matsumura |
| author_facet |
Koji Yamanoi Tsukasa Baba Kaoru Abiko Junzo Hamanishi Ken Yamaguchi Ryusuke Murakami Mana Taki Yuko Hosoe Susan K. Murphy Ikuo Konishi Masaki Mandai Noriomi Matsumura |
| author_sort |
Koji Yamanoi |
| title |
Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| title_short |
Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| title_full |
Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| title_fullStr |
Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| title_full_unstemmed |
Acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| title_sort |
acquisition of a side population fraction augments malignant phenotype in ovarian cancer |
| publisher |
Nature Portfolio |
| publishDate |
2019 |
| url |
https://doaj.org/article/44e8b3ffbba9498a88db3b0789ca4998 |
| work_keys_str_mv |
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| _version_ |
1718387994280329216 |