PTRF was first identified as Pol I and transcript release factor, which enhanced ribosomal RNA synthesis through dissociating the ternary complex of RNA polymerase I. It has
聚合酶Ⅰ和转录本释放因子(polymerase-1 and transcript release factor,PTRF/Cavin-1),最初因参与基因转录终止过程被报道,随后发现其可与细胞膜上小凹蛋白结合,通过参与细胞质膜小凹形成促进外泌体分泌,调节全身脂质代谢等。先天性...聚合酶Ⅰ和转录本释放因子(polymerase-1 and transcript release factor,PTRF/Cavin-1),最初因参与基因转录终止过程被报道,随后发现其可与细胞膜上小凹蛋白结合,通过参与细胞质膜小凹形成促进外泌体分泌,调节全身脂质代谢等。先天性全身性脂肪营养不良患者常见PTRF/Cavin-1基因突变/缺失。在胶质瘤中,PTRF/Cavin-1不仅可作为提示患者预后的标记物,还可通过影响肿瘤细胞内吞和外分泌、肿瘤脂质代谢重编程、重塑肿瘤细胞外基质等多种途径促进肿瘤恶性行为发生。本文归纳整理了PTRF/Cavin-1在胶质瘤中的多功能性,有助于全面理解其促进肿瘤发展的分子机制,开发针对PTRF/Cavin-1的胶质瘤靶向药物。展开更多
The polymerase 1 and transcript release factor(PTRF)–cytoplasmic phospholipase A2(cPLA2)phospholipid remodeling pathway facilitates tumor proliferation in glioma.Nevertheless,blockade of this pathway leads to the exc...The polymerase 1 and transcript release factor(PTRF)–cytoplasmic phospholipase A2(cPLA2)phospholipid remodeling pathway facilitates tumor proliferation in glioma.Nevertheless,blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance.Here,CD26/dipeptidyl peptidase 4(DPP4)was identified through screening of CRISPR/Cas9 libraries.Suppressing PTRF–cPLA2 signaling resulted in the activation of the epidermal growth factor receptor(EGFR)pathway through phosphatidylcholine and lysophosphatidylcholine remodeling,which ultimately increased DPP4 transcription.In turn,DPP4 interacted with EGFR and prevented its ubiquitination.Linagliptin,a DPP4 inhibitor,facilitated the degradation of EGFR by blocking its interaction with DPP4.When combined with the cPLA2 inhibitor AACOCF3,it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells.Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide.DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR.Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4–EGFR interaction.This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.展开更多
文摘PTRF was first identified as Pol I and transcript release factor, which enhanced ribosomal RNA synthesis through dissociating the ternary complex of RNA polymerase I. It has
文摘聚合酶Ⅰ和转录本释放因子(polymerase-1 and transcript release factor,PTRF/Cavin-1),最初因参与基因转录终止过程被报道,随后发现其可与细胞膜上小凹蛋白结合,通过参与细胞质膜小凹形成促进外泌体分泌,调节全身脂质代谢等。先天性全身性脂肪营养不良患者常见PTRF/Cavin-1基因突变/缺失。在胶质瘤中,PTRF/Cavin-1不仅可作为提示患者预后的标记物,还可通过影响肿瘤细胞内吞和外分泌、肿瘤脂质代谢重编程、重塑肿瘤细胞外基质等多种途径促进肿瘤恶性行为发生。本文归纳整理了PTRF/Cavin-1在胶质瘤中的多功能性,有助于全面理解其促进肿瘤发展的分子机制,开发针对PTRF/Cavin-1的胶质瘤靶向药物。
基金supported by the National Key R&D Program of China,MOST(2023YFC2510000)the Key-Area Research and Development Program of Guangdong Province(2023B1111020008)the National Natural Science Foundation of China(82373147 and 82473379).
文摘The polymerase 1 and transcript release factor(PTRF)–cytoplasmic phospholipase A2(cPLA2)phospholipid remodeling pathway facilitates tumor proliferation in glioma.Nevertheless,blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance.Here,CD26/dipeptidyl peptidase 4(DPP4)was identified through screening of CRISPR/Cas9 libraries.Suppressing PTRF–cPLA2 signaling resulted in the activation of the epidermal growth factor receptor(EGFR)pathway through phosphatidylcholine and lysophosphatidylcholine remodeling,which ultimately increased DPP4 transcription.In turn,DPP4 interacted with EGFR and prevented its ubiquitination.Linagliptin,a DPP4 inhibitor,facilitated the degradation of EGFR by blocking its interaction with DPP4.When combined with the cPLA2 inhibitor AACOCF3,it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells.Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide.DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR.Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4–EGFR interaction.This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.
