title: Gankyrin is a predictive and oncogenic factor in well-differentiated and dedifferentiated liposarcoma.
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.
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea.
authors.forename: Ju-Ae
authors.initials: JA
authors.lastname: Hwang
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Heung-Mo
authors.initials: HM
authors.lastname: Yang
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Doo-Pyo
authors.initials: DP
authors.lastname: Hong
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Samsung Advanced Institute for Health Sciences and Technology, Graduate School, Department of Health Sciences and Technology, Sungkyunkwan University.
authors.forename: Sung-Yeon
authors.initials: SY
authors.lastname: Joo
authors.affiliation: Department of Pathology, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.affiliation: Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea.
authors.forename: Joo-Hung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lazar
authors.affiliation: Division of Surgical Oncology, James Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
authors.affiliation: Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dina
authors.initials: D
authors.lastname: Lev
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Department of Surgery, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Sarcoma Research Center, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000378:metabolism; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D008080:Liposarcoma / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; C403591:PSMD10 protein, human; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex