Supplementary Figures S1-S8 from DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming

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

doi:10.1158/2159-8290.28459197

Supplementary Figures S1-S8 from DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming

https://doi.org/10.1158/2159-8290.28459197

journal contribution

posted on 2025-02-21, 18:20 authored by Ilaria Gritti, Jinkai Wan, Vajira Weeresekara, Joel M. Vaz, Giuseppe Tarantino, Tenna Holgersen Bryde, Vindhya Vijay, Ashwin V. Kammula, Prabhat Kattel, Songli Zhu, Phuong Vu, Marina Chan, Meng-Ju Wu, John D. Gordan, Krushna C. Patra, Vanessa S. Silveira, Robert T. Manguso, Marc N. Wein, Christopher J. Ott, Jun Qi, David Liu, Kei Sakamoto, Taranjit S. Gujral, Nabeel Bardeesy

Supplementary Figure S1: Validation of the specificity of the p-SIK Ser343 antibody. Supplementary Figure S2. PKAfus inactivates SIKs to support tumor cell growth in vitro and in vivo. Supplementary Figure S3. PKAfus reprograms transcription by inactivating SIK and stimulating CRTC2. Supplementary Figure S4. CRTC2/CREB mediates transcriptional regulation downstream of PKAfu. Supplementary Figure S5. CRTC2/CREB supports tumor cell growth downstream of PKAfus. Supplementary Figure S6. Primary FLC tumors show deregulation of SIK/CRTC2- controlled genes. Supplementary Figure S7. PKAfus driven tumors are sensitive to p300 inhibition. Supplementary Figure S8. PKAfus driven tumors are sensitive to p300 inhibition.

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

Alex’s Lemonade Stand Foundation for Childhood Cancer (ALSF)

Fibrolamellar Cancer Foundation (FCF)

Bertarelli Rare Cancers Fund

Novo Nordisk Fonden (NNF)

American-Italian Cancer Foundation (AICF)

History

Related Materials

1.
DOI - Is supplement to DNAJB1-PRKACA Fusion Drives Fibrolamellar Liver Cancer through Impaired SIK Signaling and CRTC2/p300-Mediated Transcriptional Reprogramming

ARTICLE ABSTRACT

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.