Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer

Patra, Krushna C.; Wang, Qi; Bhaskar, Prashanth T.; Miller, L.; Wang, Zebin; Wheaton, Will; Chandel, Navdeep S.; Laakso, Markku; Muller, William J.; Allen, Eric L.; Jha, Abhishek; Smolen, Gromoslaw A.; Clasquin, Michelle; Robey, R. Brooks; Hay, Nissim

doi:10.1016/j.ccr.2013.08.029

Cited by 25 publications

(26 citation statements)

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“…3B). One increased transcript is hexokinase 2 (HK2), which is required for both tumor initiation and maintenance in some mouse models (53). Other transcripts consistently increased included the platelet isoform of phosphofructokinase (PFKP), which plays a critical role in driving the proliferation of breast tumors (54), lactate dehydrogenase B (LDHB), which is considered essential for triple-negative breast cancer, and KRAS-dependent lung adenocarcinomas (55).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Simon

Freije

Farber

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

110

172

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Fibrolamellar hepatocellular carcinoma (FLHCC) tumors all carry a deletion of ∼400 kb in chromosome 19, resulting in a fusion of the genes for the heat shock protein, DNAJ (Hsp40) homolog, subfamily B, member 1, DNAJB1, and the catalytic subunit of protein kinase A, PRKACA. The resulting chimeric transcript produces a fusion protein that retains kinase activity. No other recurrent genomic alterations have been identified. Here we characterize the molecular pathogenesis of FLHCC with transcriptome sequencing (RNA sequencing). Differential expression (tumor vs. adjacent normal tissue) was detected for more than 3,500 genes (log2 fold change ≥1, false discovery rate ≤0.01), many of which were distinct from those found in hepatocellular carcinoma. Expression of several known oncogenes, such as ErbB2 and Aurora Kinase A, was increased in tumor samples. These and other dysregulated genes may serve as potential targets for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Simon

Freije

Farber

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

110

172

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“…Although 2-DG has been evaluated in clinical trials, its numerous cardiac side effects may preclude its use as a cancer therapeutic. However, specifi c inhibition of the hexokinase 2 isoform may be an approach to selectively target tumors, as this isoform seems especially critical in tumors but not in normal tissues ( 9 ).…”

Section: Viewsmentioning

confidence: 99%

Metabolic Dysregulation in Melanoma: Cause or Consequence?

Haq

2014

Cancer Discovery

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“…Unlike normal tissues, cancer cells are characterized by an increase in glycolysis (Warburg effect) to maximize the production of adenosine triphosphate (ATP) to meet the energy requirements for cellular proliferation [8,17]. This glycolytic phenotype of cancer cells is used in fluorodeoxyglucose positron emission tomography ( 18 FDG-PET) for diagnosis, staging, followup, detection of relapse, and monitoring tumor progression in cancer [9,[18][19][20]. Hexokinase type II, one of the four isoforms of hexokinase, is up-regulated in cancer cells [20][21][22].…”

Section: Hexokinase Inhibitorsmentioning

confidence: 99%

“…This glycolytic phenotype of cancer cells is used in fluorodeoxyglucose positron emission tomography ( 18 FDG-PET) for diagnosis, staging, followup, detection of relapse, and monitoring tumor progression in cancer [9,[18][19][20]. Hexokinase type II, one of the four isoforms of hexokinase, is up-regulated in cancer cells [20][21][22]. This overexpression can be related to an increase in gene copy number or gene promoter capacity to respond to several stimuli resulting from hypoxia or signals activated by glucose, insulin, and phorbol esters [11,17].…”

Section: Hexokinase Inhibitorsmentioning

confidence: 99%

Targeting the mitochondria in acute myeloid leukemia

Sánchez-Mendoza

Rego

2017

Appl Cancer Res

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Acute myeloid leukemia (AML) is a clonal hematologic neoplasm characterized by heterogeneity of genetic abnormalities found at diagnosis. These abnormalities serve to classify patients by risk group into low, intermediate, and high risk. It also provides specific targets for the development of new combinational therapies. However, because of the heterogeneity of genetic abnormalities, targeted therapy is not always possible. Altered mitochondrial metabolism is a common feature in cancer cells, a phenomenon first described by Otto Warburg. In AML patients, the discovery of mutations in the isocitrate dehydrogenase gene provided for the first time a link between altered mitochondrial metabolism and AML. This raised the possibility of testing drugs known as mitocans for new combinational therapeutic approaches. Mitocans are a diverse group of anti-cancer compounds that target mitochondria. They disrupt energy production leading to enhanced generation of reactive oxygen species along with the activation of the intrinsic pathway of apoptosis. The present review discusses the different types of mitocans and their mechanism of action along with preclinical and clinical studies in AML.

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Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer

Cited by 25 publications

References 0 publications

Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

Metabolic Dysregulation in Melanoma: Cause or Consequence?

Targeting the mitochondria in acute myeloid leukemia

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