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FOLR1 Regulates the Malignant Progression of Glioblastoma through the SRC/ERK1/2 Axis

Xueshan Jia¹, Weihang Liang², Junya Yang³

¹School of Public Health, Zhengzhou University, No. 100, Science Avenue, High-tech Zone, Zhengzhou, Henan 450001, China.

Combinatorial Chemistry & High Throughput Screening

|January 22, 2025

Abstract

Background:

GBM is an aggressive brain tumor with limited treatment options. Prior research has indicated FOLR1 as a pivotal gene involved in cancer pathogenesis.

Aim:

This study aimed to explore the involvement of folate receptor alpha (FOLR1) in glioblastoma (GBM) and evaluate its potential as a therapeutic target.

Objective:

This study investigated the expression pattern of FOLR1 in GBM, its impact on patient prognosis, and its role in GBM cell growth and the SRC/ERK1/2 signaling axis.

Methods:

Initially, we conducted an expression analysis of FOLR1 based on public databases and examined its expression pattern in GBM and its impact on patient prognosis. Subsequently, cell experiments were carried out to evaluate the regulation of GBM cells by differential FOLR1 expression. We then downloaded 100 FOLR1 co-expressed genes from the Linkedomics data repository and performed an enrichment analysis. Finally, the role of FOLR1 and SRC/ERK1/2 axis in GBM was analyzed again by cell experiments.

Results:

FOLR1 was found to be substantially expressed in GBM patients and was linked to a poor prognosis. Cell experiments showed that overexpression of FOLR1 promoted GBM cell growth, while low expression of FOLR1 inhibited cell growth. Additionally, genes related to FOLR1 were enriched in the lysosome, toxoplasmosis, and other pathways. This study further indicated that FOLR1 facilitates the activation of the SRC/ERK1/2 signaling pathway in GBM cells, and the attenuation of these pathways can effectively impede the malignancy-promoting effects triggered by FOLR1 in GBM cells.

Conclusions:

We revealed that FOLR1 orchestrates the malignant advancement of GBM by stimulating the SRC/ERK1/2 signaling axis, underscoring its pivotal role in the pathogenesis of GBM.

Insights

Folate receptor alpha (FOLR1) promotes glioblastoma (GBM) growth by activating the SRC/ERK1/2 pathway. Targeting FOLR1 may offer a new therapeutic strategy for this aggressive brain cancer.

Area of Science:

Oncology
Molecular Biology
Cancer Research

Background:

Glioblastoma (GBM) is an aggressive brain tumor with limited therapeutic options.
Folate receptor alpha (FOLR1) has been implicated in cancer development.
Understanding FOLR1's role in GBM is crucial for developing new treatments.

Purpose of the Study:

To investigate the expression and prognostic significance of FOLR1 in GBM.
To explore the role of FOLR1 in GBM cell growth and proliferation.
To elucidate the involvement of the SRC/ERK1/2 signaling pathway in FOLR1-mediated GBM progression.

Main Methods:

Analysis of FOLR1 expression in public databases and GBM patient samples.
In vitro cell experiments to assess the impact of FOLR1 expression on GBM cell growth.
Gene co-expression network analysis and pathway enrichment analysis.
Investigation of the SRC/ERK1/2 signaling axis in relation to FOLR1 in GBM cells.

Main Results:

FOLR1 is highly expressed in GBM and associated with poor patient prognosis.
Overexpression of FOLR1 enhances GBM cell growth; reduced expression inhibits it.
FOLR1 activates the SRC/ERK1/2 signaling pathway in GBM.
Pathway enrichment analysis revealed involvement in lysosome and toxoplasmosis pathways.

Conclusions:

FOLR1 plays a critical role in GBM pathogenesis by promoting cell growth and activating the SRC/ERK1/2 signaling axis.
Targeting FOLR1 and the SRC/ERK1/2 pathway presents a potential therapeutic strategy for GBM.

Read full analysis

Keywords:

Cell growth ERK1/2 FOLR1 SRC.glioblastoma prognosis

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