Involvement of collagen XVII in pluripotency gene expression and metabolic reprogramming of lung cancer stem cells

• Published in: Journal of biomedical science Vol. 27; no. 1; p. 5
• Main Authors: Hsu, Han-Shui, Liu, Chen-Chi, Lin, Jiun-Han, Hsu, Tien-Wei, Hsu, Jyuan-Wei, Li, Anna Fen-Yau, Hung, Shih-Chieh
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.01.2020; BioMed Central; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; A549 Cells; AKT protein; Autoantigens - biosynthesis; Biomarkers; Brain cancer; Breast cancer; Cancer genetics; Cancer treatment; Cellular Reprogramming; Chemoresistance; Collagen; Collagen Type XVII; Collagen XVII; Colorectal cancer; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genetic research; Glucose; Glucose metabolism; Glycolysis; Growth factors; Hexokinase; Hexokinase 2; HT29 Cells; Humans; Immunoglobulins; Infections; Kinases; Laminin; Life sciences; Lung cancer; Lung cancer stem cells; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Maintenance; Medical prognosis; Medical research; Metabolic reprogramming; Metabolism; Neoplasm Proteins - biosynthesis; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Non-Fibrillar Collagens - biosynthesis; Oct-4 protein; Oct4; Oxidative phosphorylation; Phenotypes; Phosphorylation; Physiological aspects; Plasmids; Pluripotency; Pluripotent Stem Cells - metabolism; Pluripotent Stem Cells - pathology; Prognosis; Proteins; Signal Transduction; Stem cells; Target recognition; Tumorigenesis; Tumorigenicity; β-Catenin; Taiwan; St Louis Missouri; United States > US; Hexokinase 2; Oct4; Metabolic reprogramming; Collagen XVII; Lung cancer stem cells
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-019-0593-y

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. 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. 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. 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.