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

Ju-Ae Hwang; Heung-Mo Yang; Doo-Pyo Hong; Sung-Yeon Joo; Yoon-La Choi; Joo-Hung Park; Alexander J Lazar; Raphael E Pollock; Dina Lev; Sung Joo Kim

doi:10.18632/oncotarget.2375

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

Oncotarget. 2014 Oct 15;5(19):9065-78. doi: 10.18632/oncotarget.2375.

Authors

Affiliations

¹ Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea. Department of Biology, Changwon National University, Changwon, Kyungnam, Republic of Korea.
² Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
³ 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.
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 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biomarkers, Tumor / biosynthesis
Biomarkers, Tumor / genetics*
Biomarkers, Tumor / metabolism
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic
Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Down-Regulation
HEK293 Cells
Humans
Liposarcoma / drug therapy
Liposarcoma / pathology*
Mice
Prognosis
Proteasome Endopeptidase Complex / biosynthesis
Proteasome Endopeptidase Complex / genetics*
Proteasome Endopeptidase Complex / metabolism
Proto-Oncogene Proteins / biosynthesis
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt / biosynthesis
RNA Interference
RNA, Small Interfering / pharmacology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
TOR Serine-Threonine Kinases / biosynthesis
Tumor Suppressor Protein p53 / biosynthesis*
Tumor Suppressor Protein p53 / metabolism
Xenograft Model Antitumor Assays

Substances

Biomarkers, Tumor
Cyclin-Dependent Kinase Inhibitor p21
PSMD10 protein, human
Proto-Oncogene Proteins
RNA, Small Interfering
Tumor Suppressor Protein p53
MTOR protein, human
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
Proteasome Endopeptidase Complex