期刊
ENDOCRINE-RELATED CANCER
卷 27, 期 11, 页码 601-614出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-19-0403
关键词
anaplastic thyroid cancer; desmoglein 2; metastasis; c-Met; tivantinib
资金
- Korea Research Institute of Bioscience and Biotechnology
- National Research Foundation of Korea - Ministry of Science, Information & Communication Technology and Future Planning [NRF-2015R1A2A2A01007743, NRF-2015M3A9D7029882, NRF-2018R1A2B2006724, NRF-2015R1D1A1A01060529]
- Korea Healthcare Technology R&D project - Ministry of Education [HI16C0312]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据