Oncotarget

Research Papers:

FOXP1 functions as an oncogene in promoting cancer stem cell-like characteristics in ovarian cancer cells

Eun Jung Choi _, Eun Jin Seo, Dae Kyoung Kim, Su In Lee, Yang Woo Kwon, Il Ho Jang, Ki-Hyung Kim, Dong-Soo Suh and Jae Ho Kim

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Oncotarget. 2016; 7:3506-3519. https://doi.org/10.18632/oncotarget.6510

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Abstract

Eun Jung Choi1, Eun Jin Seo1, Dae Kyoung Kim1, Su In Lee1, Yang Woo Kwon1, Il Ho Jang1, Ki-Hyung Kim2, Dong-Soo Suh2, and Jae Ho Kim1,3

1Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea

2Department of Obstetrics and Gynecology, School of Medicine, Pusan National University, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea

3Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Gyeongsangnam-do, Republic of Korea

Correspondence to:

Jae Ho Kim, e-mail: jhkimst@pusan.ac.kr

Keywords: cancer stem cells, epithelial ovarian cancer, FOXP1

Received: July 15, 2015     Accepted: November 21, 2015     Published: December 09, 2015

ABSTRACT

Ovarian cancer has the highest mortality rate of all gynecological cancers with a high recurrence rate. It is important to understand the nature of recurring cancer cells to terminally eliminate ovarian cancer. The winged helix transcription factor Forkhead box P1 (FOXP1) has been reported to function as either oncogene or tumor-suppressor in various cancers. In the current study, we show that FOXP1 promotes cancer stem cell-like characteristics in ovarian cancer cells. Knockdown of FOXP1 expression in A2780 or SKOV3 ovarian cancer cells decreased spheroid formation, expression of stemness-related genes and epithelial to mesenchymal transition-related genes, cell migration, and resistance to Paclitaxel or Cisplatin treatment, whereas overexpression of FOXP1 in A2780 or SKOV3 ovarian cancer cells increased spheroid formation, expression of stemness-related genes and epithelial to mesenchymal transition-related genes, cell migration, and resistance to Paclitaxel or Cisplatin treatment. In addition, overexpression of FOXP1 increased promoter activity of ABCG2, OCT4, NANOG, and SOX2, among which the increases in ABCG2, OCT4, and SOX2 promoter activity were dependent on the presence of FOXP1-binding site. In xenotransplantation of A2780 ovarian cancer cells into nude mice, knockdown of FOXP1 expression significantly decreased tumor size. These results strongly suggest FOXP1 functions as an oncogene by promoting cancer stem cell-like characteristics in ovarian cancer cells. Targeting FOXP1 may provide a novel therapeutic opportunity for developing a relapse-free treatment for ovarian cancer patients.


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