CRISPR-mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line

Ming Lin Tsai, Chia Hwa Lee, Li Chi Huang, Yu Hsin Chen, Wei Ni Liu, Chun Yu Lin, Kai Wen Hsu, Ai Wei Lee, Ching Ling Lin*

*此作品的通信作者

研究成果: Article同行評審

摘要

Squamous and anaplastic thyroid cancers are the most aggressive and life-threatening cancer types in humans, with the involvement of lymph nodes in 59% of cases and distant metastases in 26% of cases of all thyroid cancers. The median survival of squamous thyroid cancer patients is < 8 months and therefore is of high clinical concern. Here, we show that both VEGFC and VEGFR2/KDR are overexpressed in thyroid cancers, indicating that VEGF/VEGFR signaling plays a carcinogenic role in thyroid cancer development. Using CRISPR/Cas9, we established a KDR knockout (KO) SW579 squamous thyroid cancer cell line that exhibited dramatically decreased colony formation and invasion abilities (30% and 60% reduction, respectively) when compared to scrambled control cells. To validate the potential of KDR as a therapeutic target for thyroid cancers, we used the KDR RTK inhibitor sunitinib. Protein analysis and live/dead assay were performed to demonstrate that sunitinib significantly inhibited cell growth signal transduction and induced cell apoptosis of SW579 cells. These results suggest that selective targeting of KDR may have potential for development into novel anti-cancer therapies to suppress VEGF/VEGFR-mediated cancer development in patients with clinical advanced thyroid cancer.

原文English
頁(從 - 到)993-1005
頁數13
期刊FEBS Open Bio
12
發行號5
DOIs
出版狀態Published - 5月 2022

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