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Dipeptidyl Peptidase-4 Stabilizes Integrin α4β1 Complex to Promote Thyroid Cancer Cell Metastasis by Activating

Qingyuan He1,2, Hongxin Cao2, Yuelei Zhao2

  • 1Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an, P.R. China.

Thyroid : Official Journal of the American Thyroid Association
|September 27, 2022
PubMed

Insights

Dipeptidyl peptidase-4 (DPP4) promotes thyroid cancer metastasis by interacting with integrins, independent of its enzymatic activity. This pathway involves FAK/AKT, c-Jun, and TGF-β1, offering potential new therapeutic targets.

Area of Science:

  • Molecular Oncology
  • Cancer Metastasis Research

Background:

  • Metastatic disease is a primary cause of thyroid cancer mortality.
  • Mechanisms driving thyroid cancer metastasis remain incompletely understood.
  • Dipeptidyl peptidase-4 (DPP4) is implicated as a negative prognostic factor in thyroid cancer.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which DPP4 contributes to thyroid cancer cell metastasis.
  • To investigate the role of DPP4's enzymatic activity in promoting tumor metastasis.

Main Methods:

  • In vitro transwell assays to assess migration and invasion.
  • In vivo lung metastatic mouse models to evaluate metastasis.
  • Molecular and biochemical experiments to explore signaling pathways.
  • Use of DPP4 inhibitor sitagliptin.

Main Results:

  • DPP4 is upregulated in papillary thyroid cancers and correlates with lymph node metastasis and BRAF mutation.
  • DPP4 knockdown inhibits, while overexpression enhances, thyroid cancer cell metastasis.
  • Sitagliptin did not affect metastasis, indicating DPP4's role is independent of enzymatic activity.
  • DPP4 stabilizes integrin α4β1 complex, activating FAK/AKT/c-Jun signaling, leading to TGF-β1 induction and epithelial-mesenchymal transition.

Conclusions:

  • DPP4 promotes thyroid cancer metastasis via the integrin/FAK/AKT/c-Jun/TGF-β1 signaling axis.
  • This pathway represents a potential therapeutic target for managing thyroid cancer metastasis.
Keywords:
DPP4TGF-β signalingintegrinsthyroid cancertumor metastasis

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