IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma

Zhang，Xuehua1; Wang，Guoyan2; Gong，Yujiao3; Zhao，Leilei1; Song，Ping4; Zhang，He5; Zhang，Yurui1; Ju，Huanyu6; Wang，Xiaoyu7; Wang，Bin1; Ren，Huan8; Zhu，Xiao9; Dong，Yucui1

2023-05-19

10.1016/j.isci.2023.106639

iScience   影响因子和分区

2589-0042

Dual or multi-targets therapy targeting epidermal growth factor receptor variant III (EGFRvIII) and other molecular may relax the constraint for glioblastoma (GBM), putting forward the urgent requirement of finding candidate molecules. Here, the insulin-like growth factor binding protein-3 (IGFBP3) was considered a candidate, whereas the mechanisms of IGFBP3 production remain unclear. We treated GBM cells with exogenous transforming growth factor β (TGF-β) to simulate the microenvironment. We found that TGF-β and EGFRvIII transactivation induced the activation of transcription factor c-Jun, which specifically bound to the promoter region of IGFBP3 through Smad2/3 and ERK1/2 pathways and promoted the production and secretion of IGFBP3. IGFBP3 knockdown inhibited the activation of TGF-β and EGFRvIII signals and the malignant behaviors triggered by them in vitro and in vivo. Collectively, our results indicated a positive feedback loop of p-EGFRvIII/IGFBP3 under administration of TGF-β, blocking IGFBP3 may be an additional target in EGFRvIII-expressing GBM-selective therapeutic strategy.

Cancer Molecular biology

SCI

英语

通讯

Binzhou Medical University[50012304325];National Natural Science Foundation of China[61902094];National Natural Science Foundation of China[81402054];National Natural Science Foundation of China[81472367];Natural Science Foundation of Shandong Province[ZR2021MH036];

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:001000830300001

CELL PRESS

2-s2.0-85153250750

Scopus

1.Department of Immunology,Binzhou Medical University,Yantai,Shandong,264003,China
2.Clinical Laboratory of Yantai Affiliated Hospital of Binzhou Medical University,Yantai,Shandong,264199,China
3.Guangdong Provincial Key Laboratory of Biomedical Imaging,The Fifth Affiliated Hospital of Sun Yat-sen University,Zhuhai,Guangdong,519000,China
4.Department of Ophthalmology,Jiarun Hospital of Harbin,Harbin,Heilongjiang,150000,China
5.Department of Immunology,Qiqihar Medical University,Qiqihar,Heilongjiang,161000,China
6.Department of Immunology,Harbin Medical University,Harbin,Heilongjiang,150081,China
7.Department of Neurology,Hongda Hospital,Jinxiang,Shandong,272200,China
8.School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518000,China
9.School of Computer and Control Engineering,Yantai University,Yantai,Shandong,264005,China

Zhang，Xuehua,Wang，Guoyan,Gong，Yujiao,et al. IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma[J]. iScience,2023,26(5).

Zhang，Xuehua.,Wang，Guoyan.,Gong，Yujiao.,Zhao，Leilei.,Song，Ping.,...&Dong，Yucui.(2023).IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.iScience,26(5).

Zhang，Xuehua,et al."IGFBP3 induced by the TGF-β/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma".iScience 26.5(2023).