Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8322710 | The International Journal of Biochemistry & Cell Biology | 2015 | 14 Pages |
Abstract
Deregulated signaling via receptor tyrosine kinase (RTK) pathways is prevalent in numerous types of human cancers and is commonly correlated with worst prognosis, resistance to various treatment modalities and increased mortality. Likewise, hypoxic tumors are often manifested by aggressive mode of growth and progression following an adaptive genetic reprogramming with consequent transcriptional activation of genes encoding proteins, which support tumor survival under low oxygen-related conditions. Consequently, both the hypoxia-inducible factor (HIF) system, which is the major mediator of hypoxia-related signaling, and numerous RTK systems are considered critical molecular targets in current cancer therapy. It is now evident that there is an intricate molecular crosstalk between RTKs and hypoxia-related signaling in the sense that hypoxia can activate expression of particular RTKs and/or their corresponding ligands, while some RTK systems have been shown to trigger activation of the HIF machinery. Moreover, signaling regulation of some RTK systems under hypoxic conditions has also been documented to take place in a HIF-independent manner. With this review we aim at overviewing the most current observations on that topic and highlight the importance of the potential co-drugging the HIF system along with particular relevant RTKs for better tumor growth control.
Keywords
PLCγNF-kBPP2AIRSpKaMSPCAV1Neuregulin-1GDNFRACK1HNSCCPKCTGFαVEGF(R)RTKPHDBcrpHIFARNTHRECAIXVHLGTPasesEGF(R)IRESccRCCuPAPI3KGrowth arrest-specific 6HGFGTPNRG-1HUVECSfibroblast growth factor (receptor)PDGF(R)RCCmTORCSCHCCMAPKROSRTKsaryl hydrocarbon nuclear translocatorvon Hippel-LindauTOPtransforming growth factor αTopoisomeraseEMTdiacylglycerolDAGRONInsulin receptor substratesCancerNSCLCNon-small cell lung cancerClear cell renal cell carcinomaHuman umbilical vein endothelial cellsVascular smooth muscle cellsCancer stem cellsCADepidermal growth factor (receptor)Hepatocyte growth factorHypoxia-inducible factorVascular Endothelial Growth Factor (VEGF)vascular endothelial growth factor (receptor)glial-derived neurotrophic factorNuclear factor-kBPhosphatidylinositol 3-kinasephospholipase Cγurokinase-type plasminogen activatorUTR یا untranslated regions untranslated regionMicroRNAMiRNAmammalian target of rapamycinHypoxiamacrophage stimulating proteinProtein phosphatase-2Abreast cancer resistant proteinprotein kinase AProtein kinase Cmitogen-activated protein kinaseProlyl hydroxylasecaveolin-1Head and neck squamous cell carcinomaRenal cell carcinomaHepatocellular carcinomaCarbonic anhydrase IXGas6Epithelial–mesenchymal transitionGuanosine triphosphateguanosine triphosphatasesReactive oxygen speciesinsulin receptorReceptor Tyrosine Kinase
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Authors
Astrid A. Glück, Daniel M. Aebersold, Yitzhak Zimmer, Michaela Medová,