한빛사논문
- 조회983
Hyeonkyeong Kim1,2,8, Yongsik Cho1,2,8, Hyeon-Seop Kim1,2, Donghyun Kang1,2, Donghyeon Cheon2, Yi-Jun Kim3, Moon Jong Chang4, Kyoung Min Lee5, Chong Bum Chang5, Seung-Baik Kang4, Hyun Guy Kang6 & Jin-Hong Kim1,2,7,*
1Center for RNA Research, Institute for Basic Science, 08826 Seoul, South Korea. 2Department of Biological Sciences, College of Natural Sciences, Seoul National University, 08826 Seoul, South Korea.
3Department of Radiation Oncology, Ewha Womans University College of Medicine, 07985 Seoul, South Korea.
4Department of Orthopaedic Surgery, Seoul National University College of Medicine, Boramae Hospital, 07061 Seoul, South Korea.
5Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, 13620 Seongnam, South Korea.
6Orthopedic Oncology Clinic, Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, 10408 Goyang, South Korea.
7Interdisciplinary Program in Bioinformatics, Seoul National University, 08826 Seoul, South Korea.
8These authors contributed equally: Hyeonkyeong Kim, Yongsik Cho.
*Corresponding author
Abstract
Chondrosarcomas, malignant cartilaginous neoplasms, are capable of transitioning to highly aggressive, metastatic, and treatment-refractory states, resulting in significant patient mortality. Here, we aim to uncover the transcriptional program directing such tumor progression in chondrosarcomas. We conduct weighted correlation network analysis to extract a characteristic gene module underlying chondrosarcoma malignancy. Hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1) is identified as an upstream regulator that governs the malignancy gene module. HIF-2α is upregulated in high-grade chondrosarcoma biopsies and EPAS1 gene amplification is associated with poor prognosis in chondrosarcoma patients. Using tumor xenograft mouse models, we demonstrate that HIF-2α confers chondrosarcomas the capacities required for tumor growth, local invasion, and metastasis. Meanwhile, pharmacological inhibition of HIF-2α, in conjunction with the chemotherapy agents, synergistically enhances chondrosarcoma cell apoptosis and abolishes malignant signatures of chondrosarcoma in mice. We expect that our insights into the pathogenesis of chondrosarcoma will provide guidelines for the development of molecular targeted therapeutics for chondrosarcoma.
논문정보
- Research article
- 2020년 10월 (BRIC 등록일 2020-10-08)
- 국내 연구진
- 생명과학 > 노화/암생물학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기
