- 作者: Han-Shui Hsu, Chen-Chi Liu, Jiun-Han Lin, Tien-Wei Hsu, Jyuan-Wei Hsu, Anna Fen-Yau Li and Shih-Chieh Hung
- 作者服務機構: 1. Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2. Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 3. Division of Traumatology, Emergency Department, Taipei Veterans General Hospital, Taipei, Taiwan 4. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 5. Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 6. Drug Development Center, Institute of New Drug Development, Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan 7. Integrative Stem Cell Center, Department of Orthopaedics, China Medical University Hospital, Taichung, 404, Taiwan 8. Institute of Biomedical Sciences, Academia Sinica, Taipei, 105, Taiwan
- 中文摘要:
- 英文摘要:
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. - 中文關鍵字:
- 英文關鍵字: Collagen XVII, Hexokinase 2, Lung cancer stem cells, Metabolic reprogramming, Oct4