Cardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, CF24 4HQ, United Kingdom; Cardiff University School of Pharmacy and Pharmaceutical Sciences, Cardiff, CF10 3NB, United Kingdom.
Cardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, CF24 4HQ, United Kingdom.
Cancer Lett. 2023 Sep 1;571:216349. doi: 10.1016/j.canlet.2023.216349. Epub 2023 Aug 12.
Glioblastoma is the most lethal brain cancer in adults. These incurable tumors are characterized by profound heterogeneity, therapy resistance, and diffuse infiltration. These traits have been linked to cancer stem cells, which are important for glioblastoma tumor progression and recurrence. The fibroblast growth factor receptor 1 (FGFR1) signaling pathway is a known regulator of therapy resistance and cancer stemness in glioblastoma. FGFR1 expression shows intertumoral heterogeneity and higher FGFR1 expression is associated with a significantly poorer survival in glioblastoma patients. The role of FGFR1 in tumor invasion has been studied in many cancers, but whether and how FGFR1 mediates glioblastoma invasion remains to be determined. Here, we investigated the distribution and functional relevance of FGFR1 and FGFR2 in human glioblastoma xenograft models. We found FGFR1, but not FGFR2, expressed in invasive glioblastoma cells. Loss of FGFR1, but not FGFR2, significantly reduced cell migration in vitro and tumor invasion in human glioblastoma xenografts. Comparative analysis of RNA-sequencing data of FGFR1 and FGFR2 knockdown glioblastoma cells revealed a FGFR1-specific gene regulatory network associated with tumor invasion. Our study reveals new gene candidates linked to FGFR1-mediated glioblastoma invasion.
胶质母细胞瘤是成年人中最致命的脑癌。这些无法治愈的肿瘤以显著的异质性、治疗耐药性和弥漫性浸润为特征。这些特征与癌症干细胞有关,癌症干细胞对胶质母细胞瘤肿瘤的进展和复发很重要。成纤维细胞生长因子受体 1(FGFR1)信号通路是胶质母细胞瘤治疗耐药性和癌症干性的已知调节剂。FGFR1 的表达显示出肿瘤间的异质性,并且 FGFR1 表达较高与胶质母细胞瘤患者的生存率显著降低相关。FGFR1 在许多癌症中的肿瘤侵袭作用已被研究,但 FGFR1 是否以及如何介导胶质母细胞瘤侵袭仍有待确定。在这里,我们研究了 FGFR1 和 FGFR2 在人胶质母细胞瘤异种移植模型中的分布和功能相关性。我们发现 FGFR1,但不是 FGFR2,在侵袭性胶质母细胞瘤细胞中表达。FGFR1 的缺失,但不是 FGFR2 的缺失,显著降低了体外细胞迁移和人胶质母细胞瘤异种移植中的肿瘤侵袭。对 FGFR1 和 FGFR2 敲低胶质母细胞瘤细胞的 RNA 测序数据的比较分析揭示了与肿瘤侵袭相关的 FGFR1 特异性基因调控网络。我们的研究揭示了与 FGFR1 介导的胶质母细胞瘤侵袭相关的新的基因候选物。