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Updated: May 10, 2025

Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Spontaneous Murine Model of Anaplastic Thyroid Cancer

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Blocking PSMD14-mediated E2F1/ERK/AKT signaling pathways suppresses the progression of anaplastic thyroid cancer

Yuxuan Wang1, Yuansheng Duan1, Kai Yue1

  • 1Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, Tianjin 300060, China.

Cellular Signalling
|April 22, 2025
PubMed

Insights

Anaplastic thyroid cancer (ATC) cells rely on PSMD14 for growth and invasion. Inhibiting PSMD14 with thiolutin halts ATC progression and offers a potential new treatment strategy for this aggressive cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Anaplastic thyroid cancer (ATC) is highly aggressive with limited treatment options.
  • The deubiquitinating enzyme PSMD14 is a potential therapeutic target in various cancers, but its role in ATC is unclear.

Purpose of the Study:

  • To investigate the role of PSMD14 in anaplastic thyroid cancer.
  • To evaluate PSMD14 as a potential therapeutic target for ATC.

Main Methods:

  • Analysis of PSMD14 expression in ATC tissues.
  • In vitro studies involving PSMD14 depletion or inhibition with thiolutin (THL) in ATC cells.
  • In vivo studies using ATC xenografts.
  • Mechanistic studies on E2F1 stabilization and downstream signaling pathways (ERK, AKT).

Main Results:

  • PSMD14 is upregulated in ATC and associated with poor patient survival.
  • PSMD14 promotes ATC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT).
  • PSMD14 depletion or THL treatment inhibits ATC growth, invasion, induces cell cycle arrest, and apoptosis.
  • THL shows potent inhibitory effects on ATC xenografts in vivo.
  • PSMD14 stabilizes E2F1, activating ERK and AKT pathways crucial for ATC.

Conclusions:

  • PSMD14 plays a significant oncogenic role in anaplastic thyroid cancer.
  • Targeting PSMD14, for example with thiolutin, represents a promising therapeutic strategy for ATC.
Keywords:
AKTAnaplastic thyroid cancerE2F1ERKPSMD14Thiolutin

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