Dsg2-mediated c-Met activation in anaplastic thyroid cancer motility and invasion

in Endocrine-Related Cancer
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  • 1 Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea
  • 2 Department of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  • 3 Department of Biomolecular Science, KRIBB School of Bioscience, Korea University of Science & Technology, Daejeon, Republic of Korea
  • 4 Department of Medical Science, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  • 5 Department of Endocrinology and Metabolism, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  • 6 Department of Internal Medicine, Chungnam National University, School of Medicine, Daejeon, Republic of Korea
  • 7 Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  • 8 Department of Pathology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea
  • 9 Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  • 10 Daejeon Endo Internal Medicine, Daejeon, Republic of Korea

Correspondence should be addressed to K S Kim or J-K Min: kunsunkim@naver.com or jekmin@kribb.re.kr

*(K Lee and S H Lee contributed equally to this work)

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Anaplastic thyroid cancer (ATC) is a rapidly growing, highly metastatic cancer with limited therapeutic alternatives, thus targeted therapies need to be developed. This study aimed to examine desmoglein 2 (Dsg2) expression in ATC and its biological role and potential as a therapeutic target in ATC. Consequently, Dsg2 was downregulated or aberrantly expressed in ATC tissues. ATC patients with low Dsg2 expression levels also presented with distant metastasis. Dsg2 depletion significantly increased cell migration and invasion, with a relatively limited effect on ATC cell proliferation in vitro and increased distant metastasis in vivo. Dsg2 knockdown induced cell motility through the hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1 signaling axis, with no alterations in the expression of EMT-related molecules. Further, specific targeting of c-Met significantly inhibited the motility of shDsg2-depleted ATC cells. Decreased membrane Dsg2 expression increased the metastatic potential of ATC cells. These results indicate that Dsg2 plays an important role in ATC cell migration and invasiveness. Therapies targeting c-Met might be effective among ATC patients with low membrane Dsg2 expression levels, indicating that the analysis of Dsg2 expression potentially provides novel insights into treatment strategies for ATC.

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      Society for Endocrinology

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