Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte growth factor/scatter factor (HGF) is a multifunctional growth factor that is linked to the initiation and/or progression of numerous malignancies. HGF also alters cancer cell responses to DNA damaging cytotoxic agents. Many cell responses to Met activation require alterations in metabolic activity but how the metabolic machinery responds to Met activation remains poorly defined. Treating human glioblastoma cells with HGF followed by the topoisomerase inhibitor camptothecin was found to increase the activity per cell of the mitochondrial respiratory chain enzyme succinate-tetrazolium reductase (>80% increase, p < 0.05) and the tricarboxylic acid cycle enzyme succinate dehydrogenase (>25% increase, p < 0.05). Treatment with either HGF or camptothecin alone had no effect on enzyme activity. The mitochondrial enzymatic response to HGF was dose- and time-dependent with the maximum increase occurring in cells pre-treated with 30 ng/ml HGF for 48h prior to camptothecin exposure. This enzymatic response was associated with a concurrent increase in mitochondrial mass of comparable magnitude (approximately 56%, p < 0.05) as measured by fluorescent mitochondrial staining and flow cytometry. The mitochondrial mass response to HGF was prevented by the MAP-kinase pathway inhibitor PD98059 and was unaffected by the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin. These findings suggest that HGF influences cell responses to chemotherapeutic stress, in part, by altering mitochondrial functions through a MAP-kinase dependent increase in mitochondrial mass.
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PMID:Hepatocyte growth factor increases mitochondrial mass in glioblastoma cells. 1673 Jun 50

Gastrointestinal stromal tumors (GIST) are driven mostly by oncogenic KIT or PDGFRA mutations. However, in 10-15% of all GIST, no such activating mutations can be found and these tumors are classified as 'wild-type GIST' (KIT/PDGFRA wt-GIST). Subgroups of KIT/PDGFRA wt-GIST are driven by other sporadic mutations involving the RAS/RAF/MAP-kinase pathway, such as BRAF or KRAS mutations. Furthermore, KIT/PDGFRA wt-GIST are observed in the context of hereditary syndromes, such as neurofibromatosis Type 1, in which the lack of neurofibromin 1 also leads to the activation of the RAS/RAF/MAP-kinase pathway. Finally, the deficiency succinate dehydrogenase seems to play a major role in KIT/PDGFRA wt-GIST. In conclusion, KIT/PDGFRA wt-GIST belong to different subgroups defined by diverse underlying genetic alterations leading to different biological phenotypes. The vast majority of KIT/PDGFRA wt-GIST will not respond to imatinib. Further research to unravel the pathogenesis of KIT/PDGFRA wt-GIST is prerequisite to the development of effective treatment strategies.
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PMID:Classification of KIT/PDGFRA wild-type gastrointestinal stromal tumors: implications for therapy. 2583 Dec 32