PDGF-BB/PDGFR beta induces tumour angiogenesis via enhancing PKM2 mediated by the PI3K/AKT pathway in Wilms' tumour

作者全名："Sang, Bo-tao; Wang, Chang-dong; Liu, Xing; Guo, Jia-qi; Lai, Jia-yi; Wu, Xiang-mei"

作者地址："[Sang, Bo-tao; Wang, Chang-dong; Guo, Jia-qi; Lai, Jia-yi; Wu, Xiang-mei] Chongqing Med Univ, Basic Med Coll, Mol Med & Canc Res Ctr, Chongqing, Peoples R China; [Sang, Bo-tao; Guo, Jia-qi; Wu, Xiang-mei] Chongqing Med Univ, Basic Med Coll, Dept Physiol, Chongqing, Peoples R China; [Wang, Chang-dong; Lai, Jia-yi] Chongqing Med Univ, Basic Med Coll, Dept Biochem & Mol Biol, Chongqing, Peoples R China; [Liu, Xing] Chongqing Med Univ, Chongqing Childrens Hosp, Dept Pediat Urol, Chongqing, Peoples R China"

通信作者："Wu, XM (通讯作者)，Chongqing Med Univ, Basic Med Coll, Mol Med & Canc Res Ctr, Chongqing, Peoples R China.; Wu, XM (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Physiol, Chongqing, Peoples R China."

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001029952000001

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：40

期号：8

开始页：　

结束页：　

文献类型：Article

关键词：Anti-vascular therapy; Endothelial cells; PDGFR beta; PKM2; VEGFA; Wilms' tumour

摘要："Platelet-derived growth factor receptor-beta (PDGFR beta) is a critical type III receptor tyrosine kinase family member, which is involved in Wilms' tumour (WT) metastasis and aerobic glycolysis. The role of PDGFR beta in tumour angiogenesis has not been fully elucidated. Here, we examined the effect of PDGFR beta on angiogenesis in WT. First, the NCBI database integrated three datasets, GSE2712, GSE11151, and GSE73209, to screen differentially expressed genes. The R language was used to analyse the correlation between PDGFRB and vascular endothelial growth factor (VEGF). The results showed that PDGFRB, encoding PDGFR beta, was upregulated in WT, and its level was correlated with VEGFA expression. Next, PDGFR beta expression was inhibited by small interfering RNA (siRNA) or activated with the exogenous ligand PDGF-BB. The expression and secretion of the angiogenesis elated factor VEGFA in WT G401 cells were detected using Western blotting and ELISA, respectively. The effects of conditioned medium from G401 cells on endothelial cell viability, migration, invasion, the total length of the tube, and the number of fulcrums were investigated. To further explore the mechanism of PDGFR beta in the angiogenesis of WT, the expression of VEGFA was detected after blocking the phosphatidylinositol-3-kinase (PI3K) pathway and inhibiting the expression of PKM2, a key enzyme of glycolysis. The results indicated that PDGFR beta regulated the process of tumour angiogenesis through the PI3K/AKT/PKM2 pathway. Therefore, this study provides a novel therapeutic strategy to target PDGFR beta and PKM2 to inhibit glycolysis and anti-angiogenesis, thus, developing a new anti-vascular therapy."

基金机构："~Program for Youth Innovation in Future Medicine, Chongqing Medical University"

基金资助正文："& nbsp;Program for Youth Innovation in Future Medicine, Chongqing Medical University."