Abstract
Glioblastoma is the most common malignant tumor in central nervous system (CNS), and it is still insurmountable and has a poor prognosis. The proliferation and survival mechanism of glioma cells needs to be explored further for the development of glioma treatment. Hematopoietic-substrate-1 associated protein X-1 (HAX-1) has been reported as an anti-apoptosis protein that plays an important role in several malignant tumors. However, the effect and mechanism of HAX-1 in glioblastomas remains unknown. This study aimed to investigate the effect of HAX-1 in glioblastoma cells and explore the mechanism. The results of clone formation and Edu proliferation assay showed slower multiplication in HAX-1 knock-out cells. Flow cytometry showed cell cycle arrest mainly in G0/G1 phase. Apoptosis due to oxidative stress was increased after HAX-1 was knocked out. Western-blot assay exhibited that the levels of p21, Bax, and p53 proteins were significantly raised, and that the activation of the caspase cascade was enhanced in the absence of HAX-1. The degradation rate and ubiquitination of p53 declined because of the decrease in phosphorylation of proteins MDM2 and Akt1. Co-immunoprecipitation (Co-IP) and immunefluorescent co-localization assays were performed to test the influence of HAX-1 on the interaction between Akt1 and Hsp90, which is crucial for the activity of Akt1. In conclusion, this novel study suggested that HAX-1 could affect the Akt1 pathway through Hsp90. The knock-out of HAX-1 leads to the inactivity of the Ak1t/MDM2 axis, which leads to increased levels of p53, and finally generates cell cycle arrest and results in the apoptosis of glioblastoma cells.
Highlights
Glioblastoma is the most common and invasive tumor in the central nervous system (CNS)
Our results reveal a novel mechanism by which the Hematopoietic-substrate-1 associated protein X-1 (HAX-1)/heat shock protein 90 (Hsp90) complex may enhance the activation of the AKT serine/threonine kinase 1 (Akt1)/MDM2/p53 axis, and promote U118 and U87-MG survival under oxidative stress
These results show us that HAX-1 knock out causes slower proliferation of U118 and U87-MG cells
Summary
Glioblastoma is the most common and invasive tumor in the central nervous system (CNS). It is a highly aggressive, rapidly growing malignant neoplasm (Ostrom et al, 2015; Codrici et al, 2016; Maugeri et al, 2016). Relative to its rapid growth rate, its blood supply can become insufficient, causing the central part of the tumor to often suffer from ischemic necrosis. Regardless, glioblastoma cells can still proliferate rapidly in hypoxic conditions, which means some cytoprotective mechanisms exist. Studying these mechanisms may provide us novel ideas for glioblastoma therapy and treatment.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
