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
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.

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