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

Carcinoma, Squamous Cell Cell Line Humans Sunitinib Thyroid Neoplasms / genetics Vascular Endothelial Growth Factor A / genetics Vascular Endothelial Growth Factor Receptor-2 / genetics
CRISPR/Cas9 VEGFR2/KDR advanced thyroid cancer gene editing receptor tyrosine kinase inhibitor target therapy

Journal

FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716

Informations de publication

Date de publication:
05 2022
Historique:
revised: 17 02 2022
received: 01 11 2021
accepted: 18 03 2022
pubmed: 22 3 2022
medline: 6 5 2022
entrez: 21 3 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1002/2211-5463.13399 PMID: 35313079 PMC: PMC9063427
pubmed: 35313079
doi: 10.1002/2211-5463.13399
pmc: PMC9063427
doi:

Substances chimiques

Vascular Endothelial Growth Factor A 0
KDR protein, human EC 2.7.10.1
Vascular Endothelial Growth Factor Receptor-2 EC 2.7.10.1
Sunitinib V99T50803M

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

993-1005

Subventions

Organisme : Ministry of Science and Technology
ID : Most-109-2628-B-038-014
Organisme : Ministry of Science and Technology
ID : MOST-110-2628-B-038-023
Organisme : Ministry of Science and Technology
ID : MOST-109-2314-B-281-007
Organisme : Ministry of Science and Technology
ID : MOST-110-2314-B-281-004
Organisme : Cathay General Hospital
ID : CGH-MR-A10807
Organisme : Young Scholar Fellowship Program by the Ministry of Science and Technology (MOST)
ID : MOST 110-2636-B-A49-004

Informations de copyright

© 2022 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

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Auteurs

Ming-Lin Tsai (ML)

Department of General Surgery, Cathay General Hospital, Taipei, Taiwan.

Chia-Hwa Lee (CH)

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taiwan.
TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taiwan.
Ph.D. Program in Medicine Biotechnology, College of Medicine, Taipei Medical University, Taiwan.
ORCID: 0000-0002-6015-2239

Li-Chi Huang (LC)

Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
Department of Endocrinology and Metabolism, Cathay General Hospital, Taipei, Taiwan.

Yu-Hsin Chen (YH)

Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
Department of Endocrinology and Metabolism, Cathay General Hospital, Taipei, Taiwan.
Department of cytology, Cathay General Hospital, Taipei, Taiwan.

Wei-Ni Liu (WN)

School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taiwan.

Chun-Yu Lin (CY)

Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.

Kai-Wen Hsu (KW)

Institute of New Drug Development, China Medical University, Taichung City, Taiwan.
Research Center for Cancer Biology, China Medical University, Taichung City, Taiwan.

Ai-Wei Lee (AW)

Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.

Ching-Ling Lin (CL)

Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.
Department of Endocrinology and Metabolism, Cathay General Hospital, Taipei, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan.
School of Medicine, National Tsing Hua University, Hsinchu, Taiwan.

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Classifications MeSH

questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Tumeurs épidermoïdes › Carcinome épidermoïde › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Indoles › Sunitinib › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Maladies endocriniennes › Maladies de la thyroïde › Tumeurs de la thyroïde › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type A › CRISPR-mediated knockout of VEGFR2/KDR...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs aux facteurs de croissance endothéliale vasculaire › Récepteur-2 au facteur croissance endothéliale vasculaire › CRISPR-mediated knockout of VEGFR2/KDR...