A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis

Yanran Bi; Ruiling Zheng; Jiahao Hu; Ruiqing Shi; Junfeng Shi; Yutao Wang; Peng Wang; Wenyi Jiang; Gyudong Kim; Zhiguo Liu; Xiaokun Li; Li Lin

doi:10.1016/j.gendis.2023.02.035

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A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis

Full Length Articles | 更新时间：2024-02-04

- A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis
- A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis
- Genes & Diseases 2024年1卷第1期页码：479-494
- 作者机构：
  
  1. School of Pharmaceutical Science, Wenzhou Medical University,Zhejiang,Wenzhou,China,325035
  2. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea
  3. Department of Dermatology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine,Zhejiang,Wenzhou,China,325000
  4. Zhejiang Lab for Regenerative Medicine, Oujiang Laboratory,Zhejiang,Wenzhou,China,325035
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.02.035
  中图分类号：
- 纸质出版日期：2024，
  
  网络出版日期：2024-1-1，
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A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis[J]. Genes & Diseases, 2024,1(1):479-494.

Yanran Bi, Ruiling Zheng, Jiahao Hu, et al. A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis[J]. Genes & Diseases, 2024,1(1):479-494.
A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis[J]. Genes & Diseases, 2024,1(1):479-494. DOI： 10.1016/j.gendis.2023.02.035.

Yanran Bi, Ruiling Zheng, Jiahao Hu, et al. A novel FGFR1 inhibitor CYY292 suppresses tumor progression, invasion, and metastasis of glioblastoma by inhibiting the Akt/GSK3β/snail signaling axis[J]. Genes & Diseases, 2024,1(1):479-494. DOI： 10.1016/j.gendis.2023.02.035.

摘要

Abstract

Glioblastoma (GBM) is a malignant brain tumor that grows quickly

spreads widely

and is resistant to treatment. Fibroblast growth factor receptor (FGFR)1 is a receptor tyrosine kinase that regulates cellular processes

including proliferation

survival

migration

and differentiation. FGFR1 was predominantly expressed in GBM tissues

and FGFR1 expression was negatively correlated with overall survival. We rationally designed a novel small molecule CYY292

which exhibited a strong affinity for the FGFR1 protein in GBM cell lines

in vitro

. CYY292 also exerted an effect on the conserved Ser777 residue of

FGFR1

. CYY292 dose-dependently inhibited cell proliferation

epithelial–mesenchymal transition

stemness

invasion

and migration

in vitro

by specifically targeting the FGFR1/AKT/Snail pathways in GBM cells

and this effect was prevented by pharmacological inhibitors and critical gene knockdown.

In vivo

experiments revealed that CYY292 inhibited U87MG tumor growth more effectively than AZD4547. CYY292 also efficiently reduced GBM cell proliferation and increased survival in orthotopic GBM models. This study further elucidates the function of FGFR1 in the GBM and reveals the effect of CYY292

which targets FGFR1

on downstream signaling pathways directly reducing GBM cell growth

invasion

and metastasis and thus impairing the recruitment

activation

and function of immune cells.

关键词

Keywords

Blood-brain barrierEMTFGFR1FGFR1 inhibitorGlioblastoma

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