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

FEBS Open Bio

Ai‐Wei Lee¹  Ming‐Lin Tsai²  Li‐Chi Huang³  Yu‐Hsin Chen³  Ching‐Ling Lin³  Chun‐Yu Lin⁴  Kai‐Wen Hsu⁵  Chia‐Hwa Lee⁶  Wei‐Ni Liu⁶ 

[1] Department of Anatomy and Cell Biology School of Medicine College of Medicine Taipei Medical University Taiwan;Department of General Surgery Cathay General Hospital Taipei Taiwan;Department of Internal Medicine Cathay General Hospital Taipei Taiwan;Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu Taiwan;Institute of New Drug Development China Medical University Taichung City Taiwan;School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taiwan;

关键词: advanced thyroid cancer;    CRISPR/Cas9;    gene editing;    receptor tyrosine kinase inhibitor;    target therapy;    VEGFR2/KDR;   

DOI  :  10.1002/2211-5463.13399

来源: DOAJ

【 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.

【 授权许可】

Unknown