CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis

Sep 21, 2026

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Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is examined for its function in lung adenocarcinoma (LUAD), a highly aggressive cancer. Using in vitro LUAD cell assays, transcriptomic sequencing, and liquid chromatography-mass spectrometry, the study evaluates CCT6A’s effects on proliferation, invasion, and glycolysis. Co-immunoprecipitation and chromatin immunoprecipitation support a mechanism where CCT6A enhances STAT1 stability, upregulating HK2 transcription to drive aerobic glycolysis and tumor progression.

LanguageEnglish

CategoryResearch & Report

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Reading Time38 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Yu etal. Journal of Translational Medicine (2024) 22:460 [https://doi.org/10.1186/s12967-024-05284-7](https://doi.org/10.1186/s12967-024-05284-7) Journal of Translational Medicine RESEARCH Open Access CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis Shao-Kun Yu 1, Tao Yu 1, Yu-Ming Wang2, Ao Sun 1, Jia Liu 1 and Kai-Hua Lu 1* 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. Keywords CCT6A, Lung adenocarcinoma, Aerobic glycolysis, HK2, STAT1 *Correspondence: Kai-Hua Lu [lukaihua@njmu.edu.cn](lukaihua@njmu.edu.cn) 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China Introduction Lung cancer stands as the second most common cancer worldwide and the foremost cause of cancer mortality [1]. Approximately 85% of diagnosed lung cancers are non-small cell lung cancers, and lung adenocarcinoma (LUAD) is the most common subtype of them [2]. Due to its high malignancy and the limited effectiveness of chemotherapy, patients with LUAD faced grim survival outcomes. The advent of targeted therapies has markedly prolonged the survival of patients with mutations in key driver genes such as EGFR, ALK, MET, ROS1, RET, and HER2 [3]. Nevertheless, a significant fraction of LUAD patients do not possess these mutations, highlighting the © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://cre

FAQs

What role does CCT6A play in lung adenocarcinoma (LUAD)?

CCT6A is significantly overexpressed in LUAD and is associated with poorer prognosis. Its silencing suppresses LUAD cell proliferation and migration while increasing apoptosis.

How does CCT6A influence aerobic glycolysis in LUAD?

CCT6A interacts with STAT1, protecting STAT1 from ubiquitin-mediated degradation and enhancing STAT1 stability. This promotes transcription of HK2, an essential enzyme for aerobic glycolysis.

What is the main pathway proposed in the study?

The study identifies a CCT6A/STAT1/HK2 axis that reprograms glucose metabolism and thereby promotes LUAD progression.

Sep 21, 2026

Uploaded by Eliana