ATP8B1 Knockdown Activated the Choline Metabolism Pathway and Induced High-Level Intracellular REDOX Homeostasis in Lung Squamous Cell Carcinoma

Cancers

Rui Zhang¹  Yingnan Ye¹  Junya Ning¹  Xiao Zhang¹  Pengpeng Liu¹  Jinpu Yu¹  Runjiao Zhang¹  Wenwen Yu² 

[1] Cancer Molecular Diagnostics Core, National Clinical Research Center of Caner, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China;National Clinical Research Center of Caner, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Department of Immunology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China;

关键词: ATP8B1;    LUSC;    CHKA;    REDOX;   

DOI  :  10.3390/cancers14030835

来源: DOAJ

【 摘 要 】

The flippase ATPase class I type 8b member 1 (ATP8B1) is essential for maintaining the stability and polarity of the epithelial membrane and can translocate specific phospholipids from the outer membrane to the inner membrane of the cell. Although ATP8B1 plays important roles in cell functions, ATP8B1 has been poorly studied in tumors and its prognostic value in patients with lung squamous cell carcinoma (LUSC) remains unclear. By investigating the whole genomic expression profiles of LUSC samples from The Cancer Genome Atlas (TCGA) database and Tianjin Medical University Cancer Institute and Hospital (TJMUCH) cohort, we found that low expression of ATP8B1 was associated with poor prognosis of LUSC patients. The results from cellular experiments and a xenograft-bearing mice model indicated that ATP8B1 knockdown firstly induced mitochondrial dysfunction and promoted ROS production. Secondly, ATP8B1 knockdown promoted glutathione synthesis via upregulation of the CHKA-dependent choline metabolism pathway, therefore producing and maintaining high-level intracellular REDOX homeostasis to aggravate carcinogenesis and progression of LUSC. In summary, we proposed ATP8B1 as a novel predictive biomarker in LUSC and targeting ATP8B1-driven specific metabolic disorder might be a promising therapeutic strategy for LUSC.

【 授权许可】

Unknown