The Role of ALDH1A1 in Glioblastoma Proliferation and Invasion

Authors

Yu-Kai Huang
Tzu-Ming Wang
Chi-Yu Chen
Chia-Yang Li
Shu-Chi Wang
Khushboo Irshad
Yuan Pan
Kun-Che Chang

Publication Date

10-1-2024

Journal

Chemico-Biological Interactions

DOI

10.1016/j.cbi.2024.111202

PMID

39128802

PMCID

PMC12183006

PubMedCentral® Posted Date

6-23-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

High-grade gliomas, including glioblastoma multiforme (GBM), continue to be a leading aggressive brain tumor in adults, marked by its rapid growth and invasive nature. Aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), an enzyme, plays a significant role in tumor progression, yet its function in high-grade gliomas is still poorly investigated. In this study, we evaluated ALDH1A1 levels in clinical samples of GBM. We also assessed the prognostic significance of ALDH1A1 expression in GBM and LGG (low grade glioma) patients using TCGA (The Cancer Genome Atlas) database analysis. The MTT and transwell assays were utilized to examine cell growth and the invasive capability of U87 cells, respectively. We quantitatively examined markers for cell proliferation (Ki-67 and cyclin D1) and invasion (MMP2 and 9). A Western blot test was conducted to determine the downstream signaling of ALDH1A1. We found a notable increase in ALDH1A1 expression in high-grade gliomas compared to their low-grade counterparts. U87 cells that overexpressed ALDH1A1 showed increased cell growth and invasion. We found that ALDH1A1 promotes the phosphorylation of AKT, and inhibiting AKT phosphorylation mitigates the ALDH1A1's effects on tumor growth and migration. In summary, our findings suggest ALDH1A1 as a potential therapeutic target for GBM treatment.

Keywords

Humans, Glioblastoma, Cell Proliferation, Aldehyde Dehydrogenase 1 Family, Cell Line, Tumor, Retinal Dehydrogenase, Neoplasm Invasiveness, Cell Movement, Brain Neoplasms, Proto-Oncogene Proteins c-akt, Phosphorylation, Matrix Metalloproteinase 2, Cyclin D1, Signal Transduction, Glioblastoma multiforme (GBM), ALDH1A1, proliferation, invasion, AKT, Therapeutic target

Published Open-Access

yes

Recommended Citation

Huang, Yu-Kai; Wang, Tzu-Ming; Chen, Chi-Yu; et al., "The Role of ALDH1A1 in Glioblastoma Proliferation and Invasion" (2024). Faculty, Staff and Student Publications. 4943.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4943