Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer
| Autor: | Markku Laakso, Gromoslaw A. Smolen, Eric L. Allen, Abhishek K. Jha, Qi Wang, Luke L. Miller, Prashanth T. Bhaskar, Krushna C. Patra, Zebin Wang, Nissim Hay, R. Brooks Robey, Navdeep S. Chandel, Michelle Clasquin, William J. Muller, Will Wheaton |
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| Jazyk: | angličtina |
| Předmět: |
Male
medicine.medical_specialty Cancer Research Lung Neoplasms Transplantation Heterologous Breast Neoplasms Tumor initiation Biology Article Carbon utilization Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Cell Line Tumor Hexokinase Internal medicine Conditional gene knockout medicine Animals Humans Lung cancer 030304 developmental biology Mice Knockout 0303 health sciences 030302 biochemistry & molecular biology Cancer Cell Biology medicine.disease 3. Good health Disease Models Animal Hexokinase-2 Endocrinology chemistry Oncology 030220 oncology & carcinogenesis Immunology Cancer cell Cancer research Female Glycolysis |
| Zdroj: | Cancer Cell. (2):213-228 |
| ISSN: | 1535-6108 |
| DOI: | 10.1016/j.ccr.2013.06.014 |
| Popis: | SummaryAccelerated glucose metabolism is a common feature of cancer cells. Hexokinases catalyze the first committed step of glucose metabolism. Hexokinase 2 (HK2) is expressed at high level in cancer cells, but only in a limited number of normal adult tissues. Using Hk2 conditional knockout mice, we showed that HK2 is required for tumor initiation and maintenance in mouse models of KRas-driven lung cancer, and ErbB2-driven breast cancer, despite continued HK1 expression. Similarly, HK2 ablation inhibits the neoplastic phenotype of human lung and breast cancer cells in vitro and in vivo. Systemic Hk2 deletion is therapeutic in mice bearing lung tumors without adverse physiological consequences. Hk2 deletion in lung cancer cells suppressed glucose-derived ribonucleotides and impaired glutamine-derived carbon utilization in anaplerosis. |
| Databáze: | OpenAIRE |
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