HIF-1α in glioblastoma multiforme cells: Mechanisms involving the Wnt/β-catenin signaling pathway

Abstract

Glioblastoma multiforme (GBM) is a rapidly progressing brain malignancy, with its progression closely tied to a hypoxic microenvironment. Hypoxia-inducible factor-1α (HIF-1α) acts as a vital regulator in tumor adaptation to low oxygen levels, and its relationship with the Wnt/β-catenin signaling pathway exerts significant functions in the malignant properties of GBM. In this research, Western blot and qRT-PCR were applied to check β-catenin and HIF-1α expression in GBM. How HIF-1α influenced GBM cell behavior was investigated in vitro through the construction of U251 cell models with HIF-1α overexpression and knockdown, accompanied by assessments of cell proliferation, migration, invasion, and apoptosis. Additionally, co-immunoprecipitation (Co-IP) experiments were leveraged for checking the interaction of β-catenin and HIF-1α. This study demonstrated that HIF-1α and β-catenin were markedly upregulated in GBM tissues relative to normal controls, and their expression was positively correlated at the transcriptional level. In oxygen-limited environments, HIF-1α expression was significantly enhanced, and the Wnt signaling pathway was activated through stabilizing β-catenin. Functional experiments showed that HIF-1α overexpression facilitated cell proliferation, migration, and invasion, while inhibiting apoptosis; conversely, HIF-1α knockdown led to a significant reduction in these processes. Taken together, HIF-1α regulates the Wnt/β-catenin signaling pathway via its engagement with β-catenin, thereby promoting GBM proliferation and invasion, and inhibiting apoptosis. These findings emphasize the importance of HIF-1α in GBM advancement and suggest novel therapeutic strategies targeting HIF-1α and the Wnt/β-catenin pathway.