Targeting mTORC2-dependent AKT/FOXO1/RNF125 signaling exploits a therapeutic vulnerability in c-MET–activated and β-catenin–mutated hepatocellular carcinoma
Our study, for the first time, established the mTORC2/AKT/FOXO1/RNF125 axis as a critical driver and therapeutic vulnerability in c-MET-activated/β-catenin-mutated HCC. Our study filled a critical gap by defining the tumor-suppressive role of FOXO1 specifically in this HCC subtype. Furthermore, our results positioned RNF125 as a promising therapeutic target for this aggressive HCC subtype.
Authors
- Haichuan Wang (ORCID: https://orcid.org/0000-0002-6886-5698)
- Xuping Feng (ORCID: https://orcid.org/0000-0001-9575-6916)
- Yu Qiao (ORCID: https://orcid.org/0000-0002-0374-5089)
- Meng Xu (ORCID: https://orcid.org/0000-0002-8300-1054)
- Zhong Xu (ORCID: https://orcid.org/0000-0001-7565-6053)
- Yi Zhou (ORCID: https://orcid.org/0000-0001-9024-7514)
- Xue Wang (ORCID: https://orcid.org/0009-0009-4148-0788)
- Runze Shang (ORCID: https://orcid.org/0000-0002-7958-0700)
- Jennifer Haynes
- Christine Farrar (ORCID: https://orcid.org/0000-0001-8561-2257)
- Weiting Liao (ORCID: https://orcid.org/0000-0003-0667-2046)
- Guofei Cui (ORCID: https://orcid.org/0009-0005-5624-0403)
- S. Zhang
- Shuxing Zhang (ORCID: https://orcid.org/0000-0001-8994-649X)
- Diego F. Calvisi (ORCID: https://orcid.org/0000-0002-6038-8567)
- Andrew Yonemura (ORCID: https://orcid.org/0009-0009-5701-8678)
- Xin Chen (ORCID: https://orcid.org/0000-0002-9588-0164)
- Rong Li (ORCID: https://orcid.org/0000-0002-4672-7868)
- Jian Li (ORCID: https://orcid.org/0000-0001-9977-154X)
- Shu Zhang (ORCID: https://orcid.org/0000-0003-0573-2019)
- Xuemei Xie (ORCID: https://orcid.org/0000-0001-7857-0845)
- Zheng Zhang (ORCID: https://orcid.org/0000-0002-6954-8790)
- Yanhui Wu (ORCID: https://orcid.org/0000-0003-1688-5424)
Institutions
- University of Hawaiʻi at Mānoa (US)
- Huaqiao University (CN)
- University of Hawaii System (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Sichuan University (CN)
- Wuhan University (CN)
- West China Hospital of Sichuan University (CN)
- Cancer Center of Hawaii (US)
- Hubei Provincial Center for Disease Control and Prevention (CN)
- Zhongnan Hospital of Wuhan University (CN)
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Second Affiliated Hospital of Xi'an Jiaotong University (CN)
- Tongji Hospital (CN)
- University of Hawaii Cancer Center
- Huazhong University of Science and Technology (CN)
- University of Regensburg (DE)
Publication Details
- Journal
- Hepatology
- Published
- 2025-12-02
- DOI
- https://doi.org/10.1097/hep.0000000000001637
- Citations
- 1
- Primary Topic
- FOXO transcription factor regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.81