The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells

Soshi Kusunoki, Kiyoko Kato, Kouichi Tabu, Tetsunori Inagaki, Hitomi Okabe, Hiroshi Kaneda, Shin Suga, Yasuhisa Terao, Tetsuya Taga, Satoru Takeda

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Goals We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells. Method We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP(NSP) cells and used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin. Results We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells. Conclusion This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs.

Original languageEnglish
Pages (from-to)598-605
Number of pages8
JournalGynecologic Oncology
Volume129
Issue number3
DOIs
Publication statusPublished - Jun 1 2013
Externally publishedYes

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Side-Population Cells
Neoplastic Stem Cells
Endometrial Neoplasms
Epithelial-Mesenchymal Transition
Fibronectins
Genes
Real-Time Polymerase Chain Reaction
salinomycin
ras Proteins
Cell Lineage
Microarray Analysis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Obstetrics and Gynaecology

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The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells. / Kusunoki, Soshi; Kato, Kiyoko; Tabu, Kouichi; Inagaki, Tetsunori; Okabe, Hitomi; Kaneda, Hiroshi; Suga, Shin; Terao, Yasuhisa; Taga, Tetsuya; Takeda, Satoru.

In: Gynecologic Oncology, Vol. 129, No. 3, 01.06.2013, p. 598-605.

Research output: Contribution to journalArticle

Kusunoki, S, Kato, K, Tabu, K, Inagaki, T, Okabe, H, Kaneda, H, Suga, S, Terao, Y, Taga, T & Takeda, S 2013, 'The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells', Gynecologic Oncology, vol. 129, no. 3, pp. 598-605. https://doi.org/10.1016/j.ygyno.2013.03.005
Kusunoki, Soshi ; Kato, Kiyoko ; Tabu, Kouichi ; Inagaki, Tetsunori ; Okabe, Hitomi ; Kaneda, Hiroshi ; Suga, Shin ; Terao, Yasuhisa ; Taga, Tetsuya ; Takeda, Satoru. / The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells. In: Gynecologic Oncology. 2013 ; Vol. 129, No. 3. pp. 598-605.
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T1 - The inhibitory effect of salinomycin on the proliferation, migration and invasion of human endometrial cancer stem-like cells

AU - Kusunoki, Soshi

AU - Kato, Kiyoko

AU - Tabu, Kouichi

AU - Inagaki, Tetsunori

AU - Okabe, Hitomi

AU - Kaneda, Hiroshi

AU - Suga, Shin

AU - Terao, Yasuhisa

AU - Taga, Tetsuya

AU - Takeda, Satoru

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Goals We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells. Method We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP(NSP) cells and used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin. Results We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells. Conclusion This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs.

AB - Goals We previously demonstrated that side-population (SP) cells in human endometrial cancer cells (Hec1 cells) and in rat endometrial cells expressing oncogenic human K-Ras protein (RK12V cells) have features of cancer stem cells (CSCs). Hec1-SP cells showed enhanced migration and the potential to differentiate into the mesenchymal cell lineage. In this study, we analyzed the association of the epithelial-mesenchymal transition (EMT) with the properties of these endometrial CSCs. We also assessed the effects of salinomycin (a compound with EMT-specific toxicity) on the proliferative capacity, migration and invasiveness of these endometrial CSCs using Hec1-SP cells. Method We performed microarray expression analysis to screen for up-regulated genes in CSCs using a set of RK12V-SP cells and -non-SP(NSP) cells and used the Metacore package to identify the Gene GO pathway MAPs involved in the up-regulated genes. To analyze their association with EMT, the expression of several EMT associated genes in Hec1-SP cells was investigated by real time PCR and compared with that in Hec1-NSP cells. We assessed the expression of BAX, BCL2, LEF1, cyclinD and fibronectin by real time PCR. We also evaluated the viabilities, migration and invasive activities, and tumorigenicities of these SP cells and NSP cells in the presence or absence of salinomycin. Results We demonstrated that i) EMT processes were observed in both RK12V-SP cells and Hec1-SP cells, ii) the level of fibronectin was enhanced in Hec1-SP cells and salinomycin reduced the level of fibronectin expression, iii) salinomycin induced apoptosis and inhibited Wnt signaling, and iv) salinomycin inhibited the proliferation, migration, invasiveness and tumorigenicity of these SP cells. Conclusion This is the first report of an inhibitory effect of salinomycin on the properties of endometrial CSCs.

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