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| http://dx.doi.org/10.18632/oncotarget.1563 | DOI Listing |
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Dietary Folate Deficiency Promotes Lactate Metabolic Disorders to Sensitize Lung Cancer Metastasis through MTOR-Signaling-Mediated Druggable Oncotargets.
Nutrients
March 2023
Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City 242, Taiwan.
Article Synopsis
- Lactate metabolism is crucial in cancer, particularly in lung cancer, and this study explores the overlooked effects of folate deficiency on it.
- Mice fed a folate-deficient diet and implanted with lung cancer cells exhibited increased lactate production, leading to more aggressive tumor behavior and higher metastatic potential.
- Treatment with mTORC1 inhibitor rapamycin and anti-metabolic drug metformin reduced lactate-related issues and prevented lung cancer metastasis, indicating that dietary folate deficiency influences cancer progression through specific metabolic pathways.
Roles of GLUT-1 and HK-II expression in the biological behavior of head and neck cancer.
Oncotarget
April 2019
Department of Otorhinolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
The Warburg effect plays an important role in the proliferation and invasion of malignant tumors. Glucose transporter 1 and hexokinase II are two key energy transporters involved in mediating the Warburg effect. This review will analyze the mechanisms of these two markers in their effects on the biological behavior of head and neck cancer.
View Article and Find Full Text PDFThe decrease of glycolytic enzyme hexokinase 1 accelerates tumor malignancy via deregulating energy metabolism but sensitizes cancer cells to 2-deoxyglucose inhibition.
Oncotarget
April 2018
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.
Malignant tumors often display an aberrant energy metabolism that relies primarily on glycolysis to produce adenosine triphosphate (ATP) the so-called Warburg effect or aerobic glycolysis. Thus, the elucidation of this energetic alteration in malignant tumors is important in the search for more effective therapeutics against malignant cancers, the most deadly human disease. To investigate whether attenuated glycolytic activity modulates tumor progression, the effects of silencing the first and rate-limiting glycolytic enzyme hexokinase (HK) isozymes HK1 and HK2 were examined.
View Article and Find Full Text PDFUp-regulation of hexokinase II contributes to rituximab-chemotherapy resistance and is a clinically relevant target for therapeutic development.
Oncotarget
January 2018
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.
In order to identify cellular pathways associated with therapy-resistant aggressive lymphoma, we generated rituximab-resistant cell lines (RRCL) and found that the acquirement of rituximab resistance was associated with a deregulation in glucose metabolism and an increase in the apoptotic threshold leading to chemotherapy resistance. Hexokinase II (HKII), the predominant isoform overexpressed in cancer cells, has dual functions of promoting glycolysis as well as inhibiting mitochondrial-mediated apoptosis. We found that RRCL demonstrated higher HKII levels.
View Article and Find Full Text PDFA natural inhibitor of kidney-type glutaminase: a withanolide from with potent anti-tumor activity.
Oncotarget
December 2017
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
Kidney-type glutaminase (KGA), a mitochondrial enzyme converting glutamine to glutamate for energy supply, was over-expressed in many cancers and had been regarded as a promising therapeutic target in recent years. Structure-based virtual ligand screening predicted physapubescin K, a new withanolide from , to be potential KGA inhibitor. Enzyme activity inhibition assays and microscale thermophoresis experiments had demonstrated the efficiency and specificity of physapubescin K targeting KGA.
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