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CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis
- Source :
- Journal of Translational Medicine, Vol 22, Iss 1, Pp 1-15 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Background Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. Methods Our study utilized in vitro cell phenotype experiments to assess CCT6A’s impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A’s intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. Results CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD’s aerobic glycolysis and progression. Conclusion Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.
- Subjects :
- CCT6A
Lung adenocarcinoma
Aerobic glycolysis
HK2
STAT1
Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 22
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.10134e8f1d4f45819c84e1331d8192
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s12967-024-05284-7