Identification of PDLIM1 as a glioblastoma stem cell marker driving tumorigenesis and chemoresistance.

in Cell death discovery by Xiaopeng Shen, Yun Zhao, Yang Cao, Yunfeng Liu, Jian Ruan, Chunguang Wang, Meng Li, Huaizhang Jin, Shan Lu, Guoping Zhu

TLDR

  • The study found that a protein called PDLIM1 is specifically expressed in a type of brain tumor called GBM. PDLIM1 is associated with poor prognosis and advanced tumor stages. The study also found that PDLIM1 can help GBM cells grow and survive, and it can make GBM more resistant to treatment. The study suggests that PDLIM1 may be a potential target for new treatments for GBM.

Abstract

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, largely due to the presence of glioblastoma stem cells (GSCs). These cells drive tumor progression, recurrence, and chemoresistance, making them critical targets for therapy. This study aims to identify novel GSC markers for improved diagnosis and targeted treatment. We utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify PDLIM1 as a novel GSC marker. PDLIM1 was specifically expressed in GSCs and was associated with poor prognosis and advanced tumor stages. Functional assays demonstrated that PDLIM1 overexpression enhanced GBM cell proliferation, reduced apoptosis, increased GSC proportions, and promoted chemoresistance and tumorigenesis. Conversely, PDLIM1 knockdown inhibited these processes. Mechanistically, PDLIM1 was found to exert its effects likely by promoting the PI3K-AKT pathway. In conclusion, PDLIM1 may serve as a potential marker of GSCs associated with poor prognosis, tumorigenesis, and chemoresistance in GBM, representing a potential therapeutic target for improving GBM patient outcomes.

Overview

  • The study aims to identify novel GSC markers for improved diagnosis and targeted treatment of GBM. The methodology used includes scRNA-seq and bulk RNA-seq data analysis to identify PDLIM1 as a potential marker. The primary objective is to determine the role of PDLIM1 in GBM progression, recurrence, and chemoresistance, and its potential as a therapeutic target.

Comparative Analysis & Findings

  • The study found that PDLIM1 was specifically expressed in GSCs and was associated with poor prognosis and advanced tumor stages. Functional assays demonstrated that PDLIM1 overexpression enhanced GBM cell proliferation, reduced apoptosis, increased GSC proportions, and promoted chemoresistance and tumorigenesis. Conversely, PDLIM1 knockdown inhibited these processes. Mechanistically, PDLIM1 was found to exert its effects likely by promoting the PI3K-AKT pathway.

Implications and Future Directions

  • The study highlights the importance of identifying novel GSC markers for improved diagnosis and targeted treatment of GBM. The findings suggest that PDLIM1 may serve as a potential marker of GSCs associated with poor prognosis, tumorigenesis, and chemoresistance in GBM, representing a potential therapeutic target. Future research should focus on validating PDLIM1 as a GSC marker in clinical samples and developing targeted therapies that target the PI3K-AKT pathway.
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