Related Experiment Video

Updated: Jun 18, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

AKAP1 enhances glycogen accumulation and hepatocarcinogenesis through YTHDF2-mediated G6PC mRNA decay

Tao Yang1, Jiahao Zhang2, Zifeng Zhao1

  • 1Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.

Signal Transduction and Targeted Therapy
|June 16, 2026
PubMed

Insights

A kinase anchor protein 1 (AKAP1) regulates glycogen metabolism, a key factor in liver cancer (HCC) development. Inhibiting AKAP1 shows promise for HCC therapy by reducing glycogen and tumor growth.

Area of Science:

  • Oncology
  • Metabolic Research
  • Molecular Biology

Background:

  • Metabolic reprogramming of glycogen is a critical hallmark of cancer, significantly influencing tumor progression.
  • The precise molecular mechanisms driving glycogen dysregulation in cancer remain largely unidentified.

Purpose of the Study:

  • To elucidate the role of A-kinase anchor protein 1 (AKAP1) in hepatocellular carcinoma (HCC) pathogenesis.
  • To investigate the molecular mechanisms linking AKAP1 to glycogen metabolism and HCC development.
  • To evaluate the therapeutic potential of targeting AKAP1 in HCC.

Main Methods:

  • Utilized liver-specific AKAP1 depletion and overexpression mouse models for hepatocellular carcinoma (HCC) induction and spontaneous development.
  • Investigated the impact of AKAP1 on hepatic glycogen content and hepatocarcinogenesis.
  • Examined the molecular interaction between AKAP1, YTHDF2, glucose-6-phosphatase (G6PC), and protein kinase A (PKA) signaling.
  • Assessed the effect of a mitochondrial-localized AKAP1 inhibitor (AP-21) on HCC progression.

Main Results:

  • AKAP1 deficiency suppressed both chemically induced and oncogene-driven HCC by reducing hepatic glycogen.
  • AKAP1 overexpression promoted glycogen accumulation and accelerated hepatocarcinogenesis.
  • AKAP1 directly phosphorylates YTHDF2, enhancing m6A-dependent mRNA decay of G6PC, leading to glycogen accumulation and HCC.
  • AKAP1 expression is transcriptionally upregulated by MAZ in HCC cells.
  • AP-21 treatment reduced glycogen content and suppressed HCC without toxicity.

Conclusions:

  • AKAP1 plays a critical role in driving HCC through metabolic reprogramming of hepatic glycogen.
  • AKAP1-mediated regulation of G6PC via YTHDF2 is crucial for glycogen accumulation and hepatocarcinogenesis.
  • Targeting AKAP1, particularly its mitochondrial localization, represents a promising therapeutic strategy for HCC.

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