This work combines functional studies in model systems and examination of human tumor specimens to define a central oncogenic pathway driven by DNAJB1-PRKACA fusions in FLC. DNAJB1-PRKACA-mediated inactivation of the SIK stimulates CRTC2-p300-mediated transcription to drive tumor growth. The findings illuminate pathogenic mechanisms and inform therapeutic development.
DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.
DNAJB1-PRKACA融合通过损害SIK信号传导和CRTC2/p300介导的转录重编程驱动纤维板层肝癌
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作者:Gritti Ilaria, Wan Jinkai, Weeresekara Vajira, Vaz Joel M, Tarantino Giuseppe, Bryde Tenna Holgersen, Vijay Vindhya, Kammula Ashwin V, Kattel Prabhat, Zhu Songli, Vu Phuong, Chan Marina, Wu Meng-Ju, Gordan John D, Patra Krushna C, Silveira Vanessa S, Manguso Robert T, Wein Marc N, Ott Christopher J, Qi Jun, Liu David, Sakamoto Kei, Gujral Taranjit S, Bardeesy Nabeel
| 期刊: | Cancer Discovery | 影响因子: | 33.300 |
| 时间: | 2025 | 起止号: | 2025 Feb 7; 15(2):382-400 |
| doi: | 10.1158/2159-8290.CD-24-0634 | 研究方向: | 信号转导 |
| 疾病类型: | 肝癌 | ||
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