한빛사논문
- 조회778
Keun-Woo Lee1,9, So-Young Yeo1,9, Jeong-Ryeol Gong2,9, Ok-Jae Koo3, Insuk Sohn4, Woo Yong Lee5, Hee Cheol Kim5, Seong Hyeon Yun5, Yong Beom Cho5, Mi-Ae Choi1, Sugyun An2, Juhee Kim2, Chang Ohk Sung6*, Kwang-Hyun Cho2* & Seok-Hyung Kim1,7,8*
1Department of Health Science and Technology, Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea. 2Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. 3ToolGen Inc., Gasan digital 1-ro, Geumcheon, Seoul 08594, Republic of Korea. 4Arontier Inc., Gangnam-daero, Seoul, Republic of Korea. 5Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 6Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 7Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 8Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Gyeonggi-do 16419, Republic of Korea. 9These authors contributed equally: Keun-Woo Lee, So-Young Yeo, Jeong-Ryeol Gong.
*Corresponding author.
Abstract
Although stromal fibroblasts play a critical role in cancer progression, their identities remain unclear as they exhibit high heterogeneity and plasticity. Here, a master transcription factor (mTF) constructing core-regulatory circuitry, PRRX1, which determines the fibroblast lineage with a myofibroblastic phenotype, is identified for the fibroblast subgroup. PRRX1 orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-β signaling by remodeling a super-enhancer landscape. Such reprogrammed fibroblasts have myofibroblastic functions resulting in markedly enhanced tumorigenicity and aggressiveness of cancer. PRRX1 expression in cancer-associated fibroblast (CAF) has an unfavorable prognosis in multiple cancer types. Fibroblast-specific PRRX1 depletion induces long-term and sustained complete remission of chemotherapy-resistant cancer in genetically engineered mice models. This study reveals CAF subpopulations based on super-enhancer profiles including PRRX1. Therefore, mTFs, including PRRX1, provide another opportunity for establishing a hierarchical classification system of fibroblasts and cancer treatment by targeting fibroblasts.
논문정보
- Research article
- 2022년 05월 (BRIC 등록일 2022-05-24)
- 국내 연구진
- 의약학 > 종양의학
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