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Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.

Publication ,  Journal Article
Yamanoi, K; Baba, T; Abiko, K; Hamanishi, J; Yamaguchi, K; Murakami, R; Taki, M; Hosoe, Y; Murphy, SK; Konishi, I; Mandai, M; Matsumura, N
Published in: Sci Rep
October 2, 2019

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.

Duke Scholars

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 2, 2019

Volume

9

Issue

1

Start / End Page

14215

Location

England

Related Subject Headings

  • Transfection
  • Spheroids, Cellular
  • Signal Transduction
  • Side-Population Cells
  • RNA, Small Interfering
  • RNA, Neoplasm
  • RNA, Messenger
  • Prognosis
  • Phenotype
  • Ovarian Neoplasms
 

Citation

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Yamanoi, K., Baba, T., Abiko, K., Hamanishi, J., Yamaguchi, K., Murakami, R., … Matsumura, N. (2019). Acquisition of a side population fraction augments malignant phenotype in ovarian cancer. Sci Rep, 9(1), 14215. https://doi.org/10.1038/s41598-019-50794-w
Yamanoi, Koji, Tsukasa Baba, Kaoru Abiko, Junzo Hamanishi, Ken Yamaguchi, Ryusuke Murakami, Mana Taki, et al. “Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.Sci Rep 9, no. 1 (October 2, 2019): 14215. https://doi.org/10.1038/s41598-019-50794-w.
Yamanoi K, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Murakami R, et al. Acquisition of a side population fraction augments malignant phenotype in ovarian cancer. Sci Rep. 2019 Oct 2;9(1):14215.
Yamanoi, Koji, et al. “Acquisition of a side population fraction augments malignant phenotype in ovarian cancer.Sci Rep, vol. 9, no. 1, Oct. 2019, p. 14215. Pubmed, doi:10.1038/s41598-019-50794-w.
Yamanoi K, Baba T, Abiko K, Hamanishi J, Yamaguchi K, Murakami R, Taki M, Hosoe Y, Murphy SK, Konishi I, Mandai M, Matsumura N. Acquisition of a side population fraction augments malignant phenotype in ovarian cancer. Sci Rep. 2019 Oct 2;9(1):14215.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

October 2, 2019

Volume

9

Issue

1

Start / End Page

14215

Location

England

Related Subject Headings

  • Transfection
  • Spheroids, Cellular
  • Signal Transduction
  • Side-Population Cells
  • RNA, Small Interfering
  • RNA, Neoplasm
  • RNA, Messenger
  • Prognosis
  • Phenotype
  • Ovarian Neoplasms