@article{e75a8f9697f349d4be855cbd6e2c73e5,
title = "CRISPR-mediated knockout of VEGFR2/KDR inhibits cell growth in a squamous thyroid cancer cell line",
abstract = "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.",
keywords = "advanced thyroid cancer, CRISPR/Cas9, gene editing, receptor tyrosine kinase inhibitor, target therapy, VEGFR2/KDR",
author = "Tsai, {Ming Lin} and Lee, {Chia Hwa} and Huang, {Li Chi} and Chen, {Yu Hsin} and Liu, {Wei Ni} and Lin, {Chun Yu} and Hsu, {Kai Wen} and Lee, {Ai Wei} and Lin, {Ching Ling}",
note = "Funding Information: This study was supported by the Ministry of Science and Technology, grant MOST‐109‐2628‐B‐038‐014, and MOST‐110‐2628‐B‐038‐023 for Dr. Lee, grant MOST‐109‐2314‐B‐281‐007, and MOST‐110‐2314‐B‐281‐004 for Dr. Lin, Cathay General Hospital, by the grant CGH‐MR‐A10807 for both Dr. Tsai and Dr. Lee. This work was also financially supported from the Young Scholar Fellowship Program by the Ministry of Science and Technology (MOST) in Taiwan, Grant MOST 110‐2636‐B‐A49‐004 by Dr. Lin. None of the funding bodies were involved in the design of the study, the collection, analysis, and interpretation of the data, or the writing of the manuscript. We would like to acknowledge the kind service from the Facility Center of Taipei Medical University. This study was also partially supported by “TMU Research Center of Cancer Translational Medicine”, “the Center for Intelligent Drug Systems and Smart Bio‐devices (IDS2B)” and “Drug Development Center, China Medical University” from The Featured Areas Research Center Program with in the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan. Publisher Copyright: {\textcopyright} 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.",
year = "2022",
doi = "10.1002/2211-5463.13399",
language = "English",
volume = "12",
pages = "993--1005",
journal = "FEBS Open Bio",
issn = "2211-5463",
publisher = "Elsevier BV",
number = "5",
}
