Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer
By K. Patra, Qi Wang, Prashanth T. Bhaskar, L. Miller, Zebin Wang, W. Wheaton, Navdeep S. Chandel, Markku Laakso, W. Muller, Eric L. Allen and 5 more. Cancer Cell, 2013
818 citations recorded by the source corpus.
Summary Accelerated 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.
Subfields: Cancer Research, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/c531a746c124579b3eed3d220730998f5d228841
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Cancer Research
- Ralph J. Deberardinis
- Navdeep S. Chandel
- Jason W. Locasale
- Huafeng Zhang
- C. V. Dang
- Maria Liberti
- Zhaoyong Li
- B. Altman
In Molecular Biology
- Ralph J. Deberardinis
- Huafeng Zhang
- Jason W. Locasale
- Navdeep S. Chandel
- Ryuji Hamamoto
- Yusuke Nakamura
- C. V. Dang
- Maria Liberti
In Surgery
- Ryuji Hamamoto
- Yusuke Nakamura
- Ralph J. Deberardinis
- C. V. Dang
- Jason W. Locasale
- E. Lengyel
- Navdeep S. Chandel
Citations in the corpus
- Loss of BRCA1 in the cells of origin of ovarian cancer induces glycolysis: A window of opportunity for ovarian cancer chemoprevention (2017, background): “HK2 has been reported to be necessary for oncogenic transformation (34); therefore, suppressing HK2may protect against ovarian cancer.”
- The Warburg Effect: How Does it Benefit Cancer Cells? (2016, methodology): “In this scenario, the increased glucose consumption is used as a carbon source for anabolic processes needed to support cell proliferation [17, 26-32].”
- Fundamentals of cancer metabolism (2016, background): “Many tumor cells overexpressHK2, andpreclinicalmousemodels of genetically engineeredNSCLCandbreast cancer demonstrate that HK2 inhibition delays tumor progression (3).”
- Regulation of pyruvate metabolism and human disease (2013, background): “1 3 In many cancer cells, hexokinase 2, an embryonic isoform with limited expression in adult tissue, is highly upregulated in cancer [171, 172].”
- MYC, Metabolism, and Cancer. (2015, background): “Knockout of hexokinase 2 (Hk2) in genetically engineered mice significantly blunts tumorigenesis in vivo, suggesting that HK2 is an attractive therapeutic target (200).”
- KRAS: feeding pancreatic cancer proliferation (2014, neutral): “Furthermore, Hk2 has been identified as an attractive target for KRAS-driven lung cancers, as systemic whole-body deletion of HK2 in the mouse selectively targets cancer cells [74].”
- Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression (2015, background): “In addition, some metabolic enzymes in the glycolysis pathway, such as HK2, PFK1, and PKM2, also impact the oxidative or nonoxidative branch of PPP by balancing glycolytic and PPP flux [62–64].”