DNAJB1-PRKACA融合蛋白通过损害SIK信号传导以及CRTC2/p300介导的转录重编程驱动纤维板层型肝癌。
DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming.
作者信息
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
机构信息
Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, Massachusetts.
Center for Cancer Research, Center for Regenerative Medicine, Massachusetts General, Boston, Massachusetts.
出版信息
Cancer Discov. 2025 Feb 7;15(2):382-400. doi: 10.1158/2159-8290.CD-24-0634.
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.
这项研究结合了模型系统中的功能研究以及对人类肿瘤标本的检测，以确定由DNAJB1-PRKACA融合蛋白在滤泡性淋巴瘤（FLC）中驱动的核心致癌途径。DNAJB1-PRKACA介导的盐诱导激酶（SIK）失活会刺激CRTC2-p300介导的转录，从而推动肿瘤生长。这些发现揭示了致病机制，并为治疗方法的开发提供了依据。
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