Acquisition of a Side Population Fraction Augments Malignant Phenotype in Ovarian Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2019 Oct 4

PMID 31578411

Citations 8

Authors

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

Affiliations

Soon will be listed here.

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.

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