The role of ALDH1A1 in glioblastoma proliferation and invasion
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.
Authors
- Yuan Pan
- Kun‐Che Chang (ORCID: https://orcid.org/0000-0002-0871-5612)
- Chia‐Yang Li (ORCID: https://orcid.org/0000-0001-5689-9850)
- Tzu‐Ming Wang (ORCID: https://orcid.org/0000-0001-6852-0182)
- Shu‐Chi Wang (ORCID: https://orcid.org/0000-0001-9691-7507)
- Khushboo Irshad (ORCID: https://orcid.org/0000-0002-1552-3686)
- Yu-Kai Huang (ORCID: https://orcid.org/0000-0002-4606-075X)
- Chi-Yu Chen
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Kaohsiung Medical University (TW)
- University of Pittsburgh (US)
- Kaohsiung Medical University Chung-Ho Memorial Hospital (TW)
Publication Details
- Journal
- Chemico-Biological Interactions
- Published
- 2024-08-10
- DOI
- https://doi.org/10.1016/j.cbi.2024.111202
- Citations
- 4
- Primary Topic
- Caveolin-1 and cellular processes
- Type
- article
- Field-Weighted Citation Impact
- 1.30
Funders
- U.S. Department of Defense
- Eye and Ear Foundation of Pittsburgh
- Research to Prevent Blindness
- Cancer Prevention and Research Institute of Texas
- Gilbert Family Foundation
- Kaohsiung Municipal Ta-Tung Hospital
- Kaohsiung Municipal Kai-Syuan Psychiatric Hospital
- Nihon Superior
- Kaohsiung Medical University Chung-Ho Memorial Hospital
- National Institutes of Health