Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0178874 (
tumor progression
)
40,807
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Numb and Notch signalling pathways are vitally important in cell fate and differentiation. The outcome of these signalling processes is determined by a delicate balance between opposing effects of Notch and Numb. Imbalance in Numb/Notch regulation was implicated in aberrant differentiation programme and epithelial
cancer progression
and metastasis. Recent identification of Numb-interacting protein (NIP), which is also known as dual oxidase maturation factor, and was shown to associate with Numb and DUOX and promote their translocation, sheds a new light on how Numb/Notch network may be coordinated in epithelial cancers. Here, a possible link between Numb, Notch and
Dual oxidase
maturation factor is examined.
...
PMID:Interplay between Numb and Notch in epithelial cancers: role for dual oxidase maturation factor. 1952 16
Sustained generation of extracellular superoxide anions by membrane-associated NADPH oxidase-1 is a hallmark of malignant transformation. The resulting H
2
O
2
drives the proliferation of malignant cells and is converted to HOCl by a
Dual oxidase
-related peroxidase domain that acts analogously to myeloperoxidase. Whereas H
2
O
2
induces apoptosis nonselectively in nontransformed and transformed cells, HOCl selectively affects malignant cells, as the interaction between HOCl and extracellular superoxide anions allows for site-specific generation of apoptosis-inducing hydroxyl radicals. Transformed cells (early stages of
tumor progression
) and bona fide tumor cells (representing late stages of
tumor progression
) respond to exogenous HOCl or HOCl generated by professional phagocytes with induction of apoptosis. In contrast, only transformed cells have the potential to synthesize HOCl through interaction between their superoxide anions/H
2
O
2
and
Dual oxidase
-related peroxidase released by themselves or neighbouring nontransformed or transformed effector cells. Tumor cells prevent HOCl synthesis through membrane-associated catalase that decomposes H
2
O
2
, the substrate for peroxidase, and thus prevents HOCl synthesis. Elimination of malignant cells through HOCl signaling is prevented by Helicobacter pylori-associated catalase and superoxide dismutase, whereas it is enhanced by low dose irradiation and by H
2
O
2
-producing lactobacilli in the presence of myeloperoxidase. Peroxidase and catalase that are involved in the control of HOCl signaling are also affecting apoptosis-inducing pathways based on reactive nitrogen species. Modification of tumor cell proteins by HOCl enhances the establishment of a T cell response and thus might be involved in immunogenic modulation. Therefore, targeting the control of HOCl signaling system should allow one to establish novel rational therapeutic approaches.
...
PMID:HOCl and the control of oncogenesis. 2915 13
