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

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.

• Authors: Han-Shui Hsu, Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Anna Fen-Yau Li, Shih-Chieh Hung
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 27 Issue 1 Pg. 5 (Jan 13 2020) ISSN: 1423-0127 [Electronic] England
• PMID: 31928533 (Publication Type: Journal Article)

Chemical References

• Autoantigens
• Neoplasm Proteins
• Non-Fibrillar Collagens
• collagen type XVII

Topics

• A549 Cells
• Autoantigens (biosynthesis)
• Cellular Reprogramming
• Gene Expression Regulation, Neoplastic
• HT29 Cells
• Humans
• Lung Neoplasms (metabolism, pathology)
• Neoplasm Proteins (biosynthesis)
• Neoplastic Stem Cells (metabolism, pathology)
• Non-Fibrillar Collagens (biosynthesis)
• Pluripotent Stem Cells (metabolism, pathology)
• Signal Transduction