DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming
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.
Authors
- Jinkai Wan (ORCID: https://orcid.org/0000-0001-6736-0332)
- Kei Sakamoto (ORCID: https://orcid.org/0000-0001-8839-5980)
- Marc N. Wein (ORCID: https://orcid.org/0000-0002-6015-8147)
- Taranjit S. Gujral (ORCID: https://orcid.org/0000-0002-4453-3031)
- Joel Markus Vaz (ORCID: https://orcid.org/0009-0008-7177-3525)
- Songli Zhu (ORCID: https://orcid.org/0000-0001-8560-5444)
- Prabhat Kattel
- John Dozier Gordan (ORCID: https://orcid.org/0000-0001-8997-5725)
- Vanessa S. Silveira (ORCID: https://orcid.org/0000-0001-5633-9490)
- Meng‐Ju Wu (ORCID: https://orcid.org/0000-0001-6847-7065)
- Phuong Vu (ORCID: https://orcid.org/0009-0006-3846-3002)
- Ilaria Gritti (ORCID: https://orcid.org/0000-0002-7313-0450)
- Ashwin V. Kammula (ORCID: https://orcid.org/0000-0001-5284-721X)
- Krushna Chandra Patra (ORCID: https://orcid.org/0000-0002-2386-6435)
- Vindhya Vijay (ORCID: https://orcid.org/0000-0002-7886-7443)
- Jun Qi (ORCID: https://orcid.org/0000-0002-1461-3356)
- Giuseppe Tarantino (ORCID: https://orcid.org/0000-0002-6078-6856)
- Robert T. Manguso (ORCID: https://orcid.org/0000-0003-1336-413X)
- Tenna Holgersen Bryde (ORCID: https://orcid.org/0000-0003-3422-2122)
- David Liu (ORCID: https://orcid.org/0000-0003-0346-5033)
- Marina Chan
- Nabeel Bardeesy
- Christopher J. Ott
- Vajira Weeresekara
Institutions
- Broad Institute (US)
- University of Copenhagen (DK)
- Harvard University (US)
- University of California, San Francisco (US)
- Novo Nordisk Foundation (DK)
- Massachusetts General Hospital (US)
- Fred Hutch Cancer Center (US)
- Dana-Farber Cancer Institute (US)
- Center for Cancer Research (US)
- University of Cincinnati (US)
- Massachusetts Institute of Technology (US)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1158/2159-8290.cd-24-0634
- Citations
- 14
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 3.99
Funders
- Alex's Lemonade Stand Foundation for Childhood Cancer
- American-Italian Cancer Foundation
- Fibrolamellar Cancer Foundation
- Novo Nordisk
- Novo Nordisk Fonden
- National Institutes of Health
- National Cancer Institute