Spatial distribution and functional relevance of FGFR1 and FGFR2 expression for glioblastoma tumor invasion

Alshahrany, Nawal, Begum, Ayesha, Siebzehnrubl, Dorit, Jimenez-Pascual, Ana and Siebzehnrubl, Florian A. ORCID: https://orcid.org/0000-0001-8411-8775 2023. Spatial distribution and functional relevance of FGFR1 and FGFR2 expression for glioblastoma tumor invasion. Cancer Letters 571 , 216349. 10.1016/j.canlet.2023.216349

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Start Date: 2023-08-13
Publisher:	Elsevier
ISSN:	0304-3835
Funders:	MRC
Date of First Compliant Deposit:	15 August 2023
Date of Acceptance:	10 August 2023
Last Modified:	20 Sep 2023 16:48
URI:	https://orca.cardiff.ac.uk/id/eprint/161777

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