Gankyrin is a predictive and oncogenic factor in well-differentiated and dedifferentiated liposarcoma.

// Ju-Ae Hwang 1,5,* , Heung-Mo Yang 1,* , Doo-Pyo Hong 1 , Sung-Yeon Joo 1,2 , Yoon-La Choi 4 , Joo-Hung Park 5 , Alexander J. Lazar 6 , Raphael E. Pollock 7 , Dina Lev 6 and Sung Joo Kim 1,3,8 1 Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea 2 Samsung Advanced Institute for Health Sciences & Technology, Graduate School, Department of Health Sciences & Technology, Sungkyunkwan University 3 Department of Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 4 Department of Pathology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 5 Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea 6 Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA 7 Division of Surgical Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA 8 Sarcoma Research Center, Samsung Medical Center, Seoul, Republic of Korea * These authors are contributed equally to this work Correspondence: Sung Joo Kim, email: // Dina-Lev , email: // Keywords : Liposarcoma, 2-DE, Gankyrin, Predictive factor, Tumorigenesis Received : May 25, 2014 Accepted : August 20, 2014 Published : August 21, 2014 Abstract Liposarcoma is one of the most common histologic types of soft tissue sarcoma and is frequently an aggressive cancer with poor outcome. Hence, alternative approaches other than surgical excision are necessary to improve treatment of well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS). For this reason, we performed a two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry/mass spectrometry (MALDI-TOF/MS) analysis to identify new factors for WDLPS and DDLPS. Among the selected candidate proteins, gankyrin, known to be an oncoprotein, showed a significantly high level of expression pattern and inversely low expression of p53/p21 in WDLPS and DDLPS tissues, suggesting possible utility as a new predictive factor. Moreover, inhibition of gankyrin not only led to reduction of in vitro cell growth ability including cell proliferation, colony-formation, and migration, but also in vivo DDLPS cell tumorigenesis, perhaps via downregulation of the p53 tumor suppressor gene and its p21 target and also reduction of AKT/mTOR signal activation. This study identifies gankyrin, for the first time, as new potential predictive and oncogenic factor of WDLPS and DDLPS, suggesting the potential for service as a future LPS therapeutic approach.