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Updated: Jan 12, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Targeting FAM134B-DDX3X axis inhibiting AKT signaling in hepatocellular carcinoma

Jie Mo1,2, Chen Su1, Qiumeng Liu1

  • 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, P.R. China.

Cell Death & Disease
|November 6, 2025
PubMed

Insights

Family with sequence similarity 134, member B (FAM134B) stabilizes DEAD-box helicase 3 X-linked (DDX3X), activating AKT signaling and promoting hepatocellular carcinoma (HCC). This interaction reveals a new therapeutic target for HCC treatment.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Family with sequence similarity 134, member B (FAM134B) is an ER-phagy receptor linked to hepatocellular carcinoma (HCC) progression via AKT signaling.
  • The exact mechanism of FAM134B-mediated AKT activation in HCC is not fully understood.

Purpose of the Study:

  • To investigate the interaction between FAM134B and DEAD-box helicase 3 X-linked (DDX3X) in HCC.
  • To elucidate the role of this interaction in AKT signaling activation and HCC progression.

Main Methods:

  • Co-immunoprecipitation to assess protein interactions.
  • Ubiquitination assays to analyze protein degradation pathways.
  • Quantitative PCR and Western blotting to measure gene and protein expression.
  • Cell-based assays to evaluate signaling pathway activation and cell proliferation.

Main Results:

  • FAM134B directly interacts with DDX3X, inhibiting its proteasomal degradation by modulating ubiquitination.
  • Stabilized DDX3X promotes Rac Family Small GTPase 1 (Rac1) transcription, leading to AKT pathway activation.
  • A positive feedback loop exists where DDX3X enhances FAM134B transcription, further promoting HCC.
  • DDX3X is upregulated in HCC and contributes to tumor progression.

Conclusions:

  • FAM134B activates AKT signaling in HCC through the DDX3X-Rac1-AKT axis.
  • DDX3X plays a significant role in HCC progression and is a potential therapeutic target.
  • Combined FAM134B knockdown and DDX3X inhibition (e.g., RK-33) show synergistic therapeutic potential for HCC.

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