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Spontaneous Murine Model of Anaplastic Thyroid Cancer
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Dsg2-mediated c-Met activation in anaplastic thyroid cancer motility and invasion

Kyungmin Lee1,2, Sang-Hyun Lee1, Wooil Kim1,3

  • 1Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea.

Endocrine-Related Cancer
|October 6, 2020
PubMed

Insights

Desmoglein 2 (Dsg2) downregulation promotes anaplastic thyroid cancer (ATC) metastasis by increasing cell motility via the c-Met pathway. Targeting c-Met may benefit ATC patients with low Dsg2 expression.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis and limited treatment options.
  • Targeted therapies are urgently needed to address the high metastatic potential of ATC.

Purpose of the Study:

  • To investigate the expression and function of desmoglein 2 (Dsg2) in ATC.
  • To evaluate Dsg2 as a potential therapeutic target for ATC.

Main Methods:

  • Analysis of Dsg2 expression in ATC tissues.
  • In vitro and in vivo studies involving Dsg2 depletion (knockdown) in ATC cells.
  • Investigation of signaling pathways, including hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1.
  • Assessment of cell migration, invasion, proliferation, and metastasis.

Main Results:

  • Dsg2 was downregulated or aberrantly expressed in ATC tissues, correlating with distant metastasis.
  • Dsg2 depletion increased ATC cell migration and invasion, with limited impact on proliferation.
  • Dsg2 knockdown promoted cell motility via the HGFR (c-Met)/Src/Rac1 axis.
  • Targeting c-Met inhibited the motility of Dsg2-depleted ATC cells, and decreased membrane Dsg2 expression enhanced metastatic potential.

Conclusions:

  • Dsg2 plays a critical role in regulating ATC cell migration and invasiveness.
  • Therapeutic strategies targeting c-Met could be effective for ATC patients with low Dsg2 expression.
  • Dsg2 expression analysis may offer novel insights for ATC treatment strategies.
Keywords:
anaplastic thyroid cancerc-Metdesmoglein 2metastasistivantinib

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