细胞生长
癌症研究
生物
罗亚
高三尖杉酯碱
车站3
细胞迁移
自分泌信号
血小板源性生长因子受体
膜联蛋白A2
信号转导
细胞
细胞生物学
生长因子
细胞培养
受体
膜联蛋白
遗传学
髓系白血病
作者
Elena Porcù,Francesca Maule,Lorenzo Manfreda,Elena Mariotto,Silvia Bresolin,Alice Cani,Roberta Bortolozzi,Alessandro Della Puppa,Diana Corallo,Giampietro Viola,Elena Rampazzo,Luca Persano
标识
DOI:10.1016/j.trsl.2022.06.017
摘要
We previously demonstrated that Annexin A2 (ANXA2) is a pivotal mediator of the pro-oncogenic features displayed by glioblastoma (GBM) tumors, the deadliest adult brain malignancies, being involved in cell stemness, proliferation and invasion, thus negatively impacting patient prognosis. Based on these results, we hypothesized that compounds able to revert ANXA2-dependent transcriptional features could be exploited as reliable treatments to inhibit GBM cell aggressiveness by hampering their proliferative and migratory potential. Transcriptional signatures obtained by the modulation of ANXA2 activity/levels were functionally mapped through the QUADrATiC bioinformatic tool for compound identification. Selected compounds were screened by cell proliferation and migration assays in primary GBM cells, and we identified Homoharringtonine (HHT) as a potent inhibitor of GBM cell motility and proliferation, without affecting their viability. A further molecular characterization of the effects displayed by HHT, confirmed its ability to inhibit a transcriptional program involved in cell migration and invasion. Moreover, we demonstrated that the multiple antitumoral effects displayed by HHT are correlated to the inhibition of a platelet derived growth factor receptor α (PDGFRα)-dependent intracellular signaling through the impairment of Signal transducer and activator of transcription 3 (STAT3) and Ras homolog family member A (RhoA) axes. Our results demonstrate that HHT may act as a potent inhibitor of cancer cell proliferation and invasion in GBM, by hampering multiple PDGFRα-dependent oncogenic signals transduced through the STAT3 and RhoA intracellular components, finally suggesting its potential transferability for achieving an effective impairment of peculiar GBM hallmarks.
科研通智能强力驱动
Strongly Powered by AbleSci AI