CSRP2 promotes the glioblastoma mesenchymal phenotype via p130Cas-mediated NF-κB and MAPK pathways

作者：Jiawei He, Liang Zhang, Hao Xu, Chengtian Gao, Wentao Zhao, Bingchang Zhang, Wanhong Han, Wenpeng Zhao, Guowei Tan, Sifang Chen, Ping Zhong, Zhe Shen, Jian Meng, Ziqian Tang, Hanwen Lu, Xīn Gào, Zhangyu Li, Wenhua Li, Jianyao Mao, Bosen Liu, Yun‐wu Zhang, Zhanxiang Wang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2025 · DOI：10.1186/s13046-025-03484-7 · 被引用次数：3 · 研究领域：Glioma Diagnosis and Treatment、Chromatin Remodeling and Cancer、Protease and Inhibitor Mechanisms

BACKGROUND: Cysteine-rich protein 2 (CSRP2) plays a role in a variety of biological processes including cell proliferation and differentiation. However, whether and how CSRP2 participates in the malignancy of glioblastoma multiforme (GBM), including its proneural-to-mesenchymal transition (PMT), remains unclear. METHODS: CSRP2 expression in low-grade and high-grade gliomas was analyzed, and survival analyses were performed in patients with gliomas with high and low CSRP2 expression in various tumor databases. Quantitative real-time PCR (qRT-PCR) and western blotting (WB) were used to detect the expression of CSRP2 in GBM and control brain tissues. CSRP2 function in GBM was determined by a series of functional tests in vitro and in vivo. WB, co-immunoprecipitation (co-IP) and immunofluorescence were used to determine the relation between CSRP2 and p130Cas. Mechanisms of CSRP2 involvement in GBM progression were analyzed with gene set enrichment analysis and KEGG enrichment analysis in available databases. WB was used to determine the relation between CSRP2 and PMT markers, NF-κB and MAPK signaling-related proteins, and apoptosis-related proteins. Microscale thermophoresis assay was used to analyze whether mitoxantrone (MTO) and CSRP2 could bind. MTO function was determined by a series of functional tests in vitro, while the relation between MTO and PMT markers, NF-κB and MAPK signaling-related proteins, and apoptosis-related proteins was analyzed by WB in GBM cell lines stably...