Oxidative Phosphorylation Regulates the Metabolism of Lung Squamous Cell Carcinoma
10.13865/j.cnki.cjbmb.2025.02.1491
- VernacularTitle:氧化磷酸化信号参与肺鳞状细胞癌代谢调节
- Author:
Liang WANG
1
;
Shan-Yuan ZHANG
1
;
Yue YANG
1
;
Yuan-Yuan MA
1
Author Information
1. 北京大学肿瘤医院暨北京市肿瘤防治研究所胸外二科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京 100142
- Publication Type:Journal Article
- Keywords:
lung squamous cell carcinoma(LUSC);
metabolism;
oxidative phosphorylation(OX-PHOS);
cancer stem cells
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(3):437-445
- CountryChina
- Language:Chinese
-
Abstract:
Metabolic reprogramming is a crucial feature of cancer.Among various metabolic processes,oxidative phosphorylation(OXPHOS)metabolism serves as the primary biochemical pathway for energy production and significantly influences tumorigenesis and tumor development.Therefore,this study aims to explore the impact of the metabolic characteristics of lung squamous cell carcinoma(LUSC)on its ma-lignant properties.By analyzing the single-cell transcriptome sequencing data of LUSC,lung adenocarci-noma,and normal lung tissues from the gene expression profile database,it was found that the OXPHOS signaling pathway and molecules related to ATP synthesis were remarkably enriched in LUSC tissues.Based on the OXPHOS signal intensity score,LUSC cells were classified into OXPHOShigh and OXPH-OSlow groups.Bioinformatics analysis revealed that 126 transcription factors were highly expressed in both LUSC tumor tissues and the OXPHOShigh group.Notably,the expression levels of cancer stem cell-related signals(such as SOX2,SOX9,POU2F1,CDX1,ARID3A,EZH2,and KLF5)were significantly en-hanced in the OXPHOShigh cell subset(P＜0.05).Treatment of LUSC cells with an OXPHOS antagonist significantly inhibited the sphere formation rate of H520 and SKMES-1 cells,which is a key characteristic of cancer stemness(P＜0.05).Analysis of cell-cell communication data from the LUSC single-cell tran-scriptome indicated that the signal emission and reception in OXPHOShigh cells were stronger than those in OXPHOSlow cells.Moreover,fibroblasts showed significant interaction with OXPHOShigh-LUSC cells.Co-culture of LUSC cell lines H520 and SKMES-1 with human lung fibroblast-like cell lines significantly in-creased the sphere formation rate of tumor cells(P＜0.05).Additionally,the levels of ATP,NADH-ac-tive enzymes,and reactive oxygen species(ROS)in co-cultured H520 and SKMES-1 cells were signifi-cantly elevated(P＜0.05).The results of this study confirm that the OXPHOS pathway is a key signal involved in LUSC metabolism,which is closely associated with the characteristics of cancer stem cells and the regulatory signals of fibroblast interactions.This finding holds promises for providing novel strategies for tumor treatment.
