Related Experiment Video

Updated: May 16, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

542

Syntaxin-6 mediated autophagy confers lenvatinib resistance in hepatocellular carcinoma

Guo-Pei Zhang1, Ze-Bing Song1, De-Hua Chen1

  • 1Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

Oncogene
|April 2, 2025
PubMed

Insights

Syntaxin-6 (STX6) drives lenvatinib resistance in hepatocellular carcinoma (HCC) by promoting autophagy. Targeting STX6-mediated autophagy may overcome drug resistance in HCC patients.

Area of Science:

  • Hepatocellular Carcinoma Research
  • Cancer Biology
  • Drug Resistance Mechanisms

Background:

  • Lenvatinib is a first-line treatment for inoperable hepatocellular carcinoma (HCC).
  • Acquired and intrinsic drug resistance to lenvatinib limits its therapeutic efficacy.
  • Autophagy, a cellular degradation process, is implicated in tumor survival under stress and may contribute to drug resistance.

Purpose of the Study:

  • To elucidate the role of autophagy in lenvatinib resistance in HCC.
  • To identify key regulators of lenvatinib resistance mediated by autophagy.
  • To investigate Syntaxin-6 (STX6) as a potential therapeutic target for overcoming lenvatinib resistance.

Main Methods:

  • Establishment of lenvatinib-resistant HCC cell lines and xenograft mouse models.
  • In vitro functional restoration assays and autophagic flux detection.
  • Co-immunoprecipitation assays and mass spectrometry to identify protein interactions.

Main Results:

  • Syntaxin-6 (STX6)-mediated autophagy was demonstrated to induce lenvatinib resistance in HCC cells.
  • STX6 interacts with Beclin1, VTI1A, and VAMP3, facilitating autophagy and promoting HCC proliferation, migration, and invasion.
  • Elevated STX6 expression in HCC tissues correlated with poor patient outcomes and reduced efficacy of lenvatinib adjuvant therapy.

Conclusions:

  • STX6-mediated autophagy is a critical mechanism underlying lenvatinib resistance in HCC.
  • STX6 represents a promising therapeutic target to enhance lenvatinib efficacy in HCC treatment.
  • Targeting STX6 could offer a novel strategy to overcome drug resistance in hepatocellular carcinoma.

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