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Dynorphin B Promotes Autophagy and Cytotoxicity in Thyroid Cancer Cells via the mTORC1-TFE3 Axis

Xuesong Wu1, Xuesong Zhai1, Lizhen Ren2

  • 1Department of Head and Neck Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, China.

Journal of Biochemical and Molecular Toxicology
|June 9, 2026
PubMed

Insights

Dynorphin B induces thyroid cancer cell death by activating autophagy via the mTORC1-TFE3 pathway. This peptide shows potential for thyroid cancer therapy by modulating cell fate.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Autophagy plays a dual role in thyroid cancer, supporting survival or inducing cell death.
  • Targeting autophagy presents a promising therapeutic strategy for thyroid cancer.
  • The specific role and mechanisms of Dynorphin B in thyroid cancer remain to be fully elucidated.

Purpose of the Study:

  • To investigate the effects of Dynorphin B on thyroid cancer cells (TPC-1).
  • To elucidate the molecular mechanisms underlying Dynorphin B's action, focusing on autophagy and cytotoxicity.
  • To explore the potential therapeutic implications of Dynorphin B in thyroid cancer.

Main Methods:

  • Utilized TPC-1 thyroid cancer cell lines.
  • Assessed autophagy markers (LC3-II/I ratio, p62 degradation, monodansylcadaverine staining).
  • Measured cytotoxicity, mitochondrial membrane potential, ATP production, and oxidative stress (8-OHdG, SOD activity).
  • Investigated the mTORC1-TFE3 signaling pathway (p-S6K, TFE3 phosphorylation and nuclear translocation).
  • Performed chromatin immunoprecipitation and luciferase assays to confirm TFE3 transcriptional activity.
  • Conducted immunohistochemical analysis of KOR-1 expression in clinical thyroid tissue samples.

Main Results:

  • Dynorphin B triggered autophagic flux and increased autophagosome formation in TPC-1 cells.
  • Dynorphin B induced dose-dependent cytotoxicity, disrupted mitochondrial function, and increased oxidative stress.
  • Dynorphin B inhibited mTORC1, leading to TFE3 dephosphorylation and nuclear translocation.
  • TFE3 activation by Dynorphin B upregulated key autophagy and lysosomal genes (ATG5, LC3, LAMP1, CTSD).
  • TFE3 knockdown abrogated Dynorphin B's effects, confirming its essential role.
  • Lower KOR-1 expression was observed in malignant thyroid tissues compared to normal tissues.

Conclusions:

  • Dynorphin B modulates autophagy and cytotoxicity in thyroid cancer cells through the mTORC1-TFE3 signaling axis.
  • Dynorphin B's mechanism involves TFE3-mediated transcriptional activation of autophagy and lysosomal genes.
  • These findings highlight Dynorphin B's potential as a therapeutic agent for thyroid cancer by influencing cancer cell fate.
Keywords:
Dynorphin BTFE3autophagymTORC1thyroid cancer

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