The role of ALDH1A1 in glioblastoma proliferation and invasion

被引:4
作者
Huang, Yu-Kai [1 ,2 ]
Wang, Tzu-Ming [1 ]
Chen, Chi-Yu [3 ]
Li, Chia-Yang [2 ]
Wang, Shu-Chi [4 ]
Irshad, Khushboo [5 ]
Pan, Yuan [5 ]
Chang, Kun-Che [2 ,3 ,6 ,7 ]
机构
[1] Kaohsiung Med Univ Hosp, Dept Surg, Div Neurosurg, Kaohsiung 80708, Taiwan
[2] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung 80708, Taiwan
[3] Univ Pittsburgh, Louis J Fox Ctr Vis Restorat, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA
[4] Kaohsiung Med Univ, Ctr Liquid Biopsy & Cohort Res, Dept Med Lab Sci & Biotechnol, Kaohsiung 80708, Taiwan
[5] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA
[6] Univ Pittsburgh, Sch Med, Dept Neurobiol, Ctr Neurosci, Pittsburgh, PA 15213 USA
[7] Univ Pittsburgh, Swanson Sch Engn, Dept Bioengn, Pittsburgh, PA 15261 USA
关键词
Glioblastoma multiforme (GBM); Proliferation; Invasion; AKT; Therapeutic target; CANCER-CELLS; CYCLIN D1; EXPRESSION; AKT; NECROPTOSIS; ACTIVATION; PATHWAY;
D O I
10.1016/j.cbi.2024.111202
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:9
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