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Lee, Keun-Woo; Yeo, So-Young; Gong, Jeong-Ryeol; Koo, Ok-Jae; Sohn, Insuk; Lee, Woo Yong; Kim, Hee Cheol; Yun, Seong Hyeon; Cho, Yong Beom; Choi, Mi-Ae; An, Sugyun; Kim, Juhee; Sung, Chang Ohk; Cho, Kwang-Hyun; Kim, Seok-Hyung
Nature communications, 05/2022, Letnik: 13, Številka: 1Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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