Although the majority of adult tissues express only hexokinase 1 (HK1) for glycolysis, most cancers express hexokinase 2 (HK2) and many coexpress HK1 and HK2. In contrast to HK1HK2 cancers, HK1HK2 cancer subsets are sensitive to cytostasis induced by HK2 knockdown and are also sensitive to synthetic lethality in response to the combination of HK2 knockdown, an oxidative phosphorylation (OXPHOS) inhibitor diphenyleneiodonium (DPI), and a fatty acid oxidation (FAO) inhibitor perhexiline (PER). The majority of human multiple myeloma cell lines are HK1HK2.
View Article and Find Full Text PDFBackground: Precision medicine therapies require identification of unique molecular cancer characteristics. Hexokinase (HK) activity has been proposed as a therapeutic target; however, different hexokinase isoforms have not been well characterized as alternative targets. While HK2 is highly expressed in the majority of cancers, cancer subtypes with differential HK1 and HK2 expression have not been characterized for their sensitivities to HK2 silencing.
View Article and Find Full Text PDFAlthough absent in most adult tissues, hexokinase 2 (HK2) is expressed in a majority of tumors and contributes to increased glucose consumption and to in vivo tumor F-FDG PET signaling. Both HK2 knockdown and knockout approaches were used to investigate the role of HK2 in cancer cell proliferation, in vivo xenograft tumor progression and F-FDG tumor accumulation. BioProfiler analysis monitored cell culture glucose consumption and lactate production; F-FDG PET/CT monitored in vivo tumor glucose accumulation.
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