BMB Reports 2018; 51(10): 514-519  https://doi.org/10.5483/BMBRep.2018.51.10.042
TRRAP stimulates the tumorigenic potential of ovarian cancer stem cells
Kyung Taek Kang1, Yang Woo Kwon1, Dae Kyoung Kim1, Su In Lee1, Ki-Hyung Kim2, Dong-Soo Suh2 and Jae Ho Kim1,3,*
Departments of 1Physiology and 2Obstetrics and Gynecology, School of Medicine, Pusan National University, Yangsan 50612, 3Research Institute of Convergence Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 50612, Korea
Correspondence to: Tel: +82-51-510-8073; Fax: +82-51-510-8076; E-mail: jhkimst@pusan.ac.kr
Received: February 22, 2018; Revised: March 19, 2018; Accepted: May 15, 2018; Published online: October 31, 2018.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Ovarian cancer is the most fatal gynecological malignancy in women and identification of new therapeutic targets is essential for the continued development of therapy for ovarian cancer. TRRAP (transformation/transcription domain-associated protein) is an adaptor protein and a component of histone acetyltransferase complex. The present study was undertaken to investigate the roles played by TRRAP in the proliferation and tumorigenicity of ovarian cancer stem cells. TRRAP expression was found to be up-regulated in the sphere cultures of A2780 ovarian cancer cells. Knockdown of TRRAP significantly decreased cell proliferation and the number of A2780 spheroids. In addition, TRRAP knockdown induced cell cycle arrest and increased apoptotic percentages of A2780 sphere cells. Notably, the mRNA levels of stemness-associated markers, that is, OCT4, SOX2, and NANOG, were suppressed in TRRAP-silenced A2780 sphere cells. In addition, TRRAP overexpression increased the mRNA level of NANOG and the transcriptional activity of NANOG promoter in these cells. Furthermore, TRRAP knockdown significantly reduced tumor growth in a murine xenograft transplantation model. Taken together, the findings of the present study suggest that TRRAP plays an important role in the regulation of the proliferation and stemness of ovarian cancer stem cells.
Keywords: Cancer stem cells, Ovarian cancer, Spheroid, TRRAP


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Funding Information
  • National Research Foundation of Korea(NRF)
      10.13039/501100003725
      NRF-2015R1A5A2009656
  • Ministry of Education, Science and Technology(Korean Ministry of Education, Science and Technology)
      10.13039/501100004085
      NRF-2016R1D1A1B03935769
  • Ministry of Health and Welfare(Ministry of Health, Welfare and Family Affairs)
      10.13039/501100003625
      HI17C1635

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