1. Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells
- Author
-
Jiun Han Lin, Jyuan Wei Hsu, Shih-Chieh Hung, Anna Fen Yau Li, Chen Chi Liu, Tien Wei Hsu, and Han Shui Hsu
- Subjects
Pluripotent Stem Cells ,Lung Neoplasms ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,lcsh:Medicine ,Oxidative phosphorylation ,Oct4 ,Biology ,Autoantigens ,Downregulation and upregulation ,Cancer stem cell ,Gene expression ,medicine ,Humans ,Pharmacology (medical) ,Glycolysis ,Lung cancer ,Molecular Biology ,Collagen XVII ,Lung cancer stem cells ,Research ,Biochemistry (medical) ,lcsh:R ,Metabolic reprogramming ,Cell Biology ,General Medicine ,Non-Fibrillar Collagens ,medicine.disease ,Cellular Reprogramming ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,Hexokinase-2 ,A549 Cells ,Cancer research ,Neoplastic Stem Cells ,Hexokinase 2 ,Stem cell ,HT29 Cells ,Signal Transduction - Abstract
Background Recent advancements in cancer biology field suggest that glucose metabolism is a potential target for cancer treatment. However, little if anything is known about the metabolic profile of cancer stem cells (CSCs) and the related underlying mechanisms. Methods The metabolic phenotype in lung CSC was first investigated. The role of collagen XVII, a putative stem cell or CSC candidate marker, in regulating metabolic reprogramming in lung CSC was subsequently studied. Through screening the genes involved in glycolysis, we identified the downstream targets of collagen XVII that were involved in metabolic reprogramming of lung CSCs. Collagen XVII and its downstream targets were then used to predict the prognosis of lung cancer patients. Results We showed that an aberrant upregulation of glycolysis and oxidative phosphorylation in lung CSCs is associated with the maintenance of CSC-like features, since blocking glycolysis and oxidative phosphorylation reduces sphere formation, chemoresistance, and tumorigenicity. We also showed that the Oct4-hexokinase 2 (HK2) pathway activated by collagen XVII-laminin-332 through FAK-PI3K/AKT-GSB3β/β-catenin activation induced the upregulation of glycolysis and maintenance of CSC-like features. Finally, we showed that collagen XVII, Oct4, and HK2 could be valuable markers to predict the prognosis of lung cancer patients. Conculsions These data suggest the Oct4-HK2 pathway regulated by collagen XVII plays an important role in metabolic reprogramming and maintenance of CSC-like features in lung CSCs, which may aid in the development of new strategies in cancer treatment.
- Published
- 2020