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您的检索式：作者名="Jiami Huang"
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| 1 | The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells显示文摘Background:Chemotherapy resistance is a primary reason of ovarian cancer therapy failure;hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets.Methods:RNA sequencing of cisplatin-resistant and sensitive(chemoresis-tant and chemosensitive,respectively)ovarian cancer organoids was performed,followed by detection of the expression level of fibrillin-1(FBN1)in organoids and clinical specimens of ovarian cancer.Subsequently,glucose metabolism,angiogenesis,and chemosensitivity were analyzed in structural glycoprotein FBNl-knockout cisplatin-resistant ovarian cancer organoids and cell lines.To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer,immunoprecipitation,silver nitrate staining,mass spectrometry,immunofluorescence,Western blotting,and Forister resonance energy transfer-fluorescence lifetime imaging analyses were performed,followed by in vivo assays using vertebrate model systems of nude mice and zebrafish.Results:FBN1 expression was significantly enhanced in cisplatin-resistant ovar-ian cancer organoids and tissues,indicating that FBNI might be a key factor in chemoresistance of ovarian cancer.We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo,which promoted the cisplatin-resistance of ovarian cancer.Knockout of FBN1 combined with treat-ment of the antiangiogenic drug apatinib improved the cisplatin-sensitivity of ovarian cancer cells.Mechanistically,FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2(VEGFR2)at the Tyrl054 residue,which activated its downstream focal adhesion kinase(FAK)/protein kinase B(PKB or AKT)pathway,induced the phosphorylation of signal transducer and activator of transcription 2(STAT2)at the tyrosine residue 690(Tyr690),pro-moted the nuclear translocation of STAT2,and ultimately altered the expression of genes associated with STAT2-mediated angiogenesis and glycolysis.Conclusions:The FBN1/VEGFR2/STAT2 signaling axis may induce chemore-sistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis.The present study suggested a novel FBNl-targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer. | Ziliang Wang Wei Chen Ling Zuo Midie Xu Yong Wu Jiami Huang Xu Zhang Yongheng Li Jing Wang Jing Chen Husheng Wang Huizhen Sun | 2022 | Cancer Communications2022，42，3： | 3 |
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