- Tytuł:
- TGF beta signalling and its role in tumour pathogenesis.
- Autorzy:
-
Kaminska, Bozena
Wesolowska, Aleksandra
Danilkiewicz, Malgorzata - Powiązania:
- https://bibliotekanauki.pl/articles/1041410.pdf
- Data publikacji:
- 2005
- Wydawca:
- Polskie Towarzystwo Biochemiczne
- Tematy:
-
Smad propteins
RNA interference.
TGF beta signal transduction
tumour invasion
cancer therapy
MAP kinases - Opis:
- Transforming growth factor beta (TGF-β) is a multifunctional cytokine involved in the regulation of cell proliferation, differentiation and survival/or apoptosis of many cells. Knock-out experiments in mice for the three isoforms of TGF-β have demonstrated their importance in regulating inflammation and tissue repair. TGF-β is implicated in the pathogenesis of human diseases, including tissue fibrosis and carcinogenesis. TGF-β receptors act through multiple intracellular pathways. Upon binding of TGF-β with its receptor, receptor-regulated Smad2/3 proteins become phosphorylated and associate with Smad4. Such complex translocates to the nucleus, binds to DNA and regulates transcription of specific genes. Negative regulation of TGF-β/Smad signalling may occur through the inhibitory Smad6/7. Furthermore, TGF-β-activated kinase-1 (TAK1) is a component of TGF-β signalling and activates stress-activated kinases: p38 through MKK6 or MKK3 and c-Jun N-terminal kinases (JNKs) via MKK4. In the brain TGF-β, normally expressed at the very low level, increases dramatically after injury. Increased mRNA levels of the three TGF-β isoforms correlate with the degree of malignancy of human gliomas. TGF-βs are secreted as latent precursors requiring activation into the mature form. TGF-β may contribute to tumour pathogenesis by direct support of tumour growth and influence on local microenvironment, resulting in immunosuppression, induction of angiogenesis, and modification of the extracellular matrix. TGF-β1,2 may stimulate production of vascular endothelial growth factor (VEGF) as well as plasminogen activator inhibitor (PAI-I), that are involved in vascular remodelling occurring during angiogenesis. Blocking of TGF-β action inhibits tumour viability, migration, metastases in mammary cancer, melanoma and prostate cancer model. Reduction of TGF-β production and activity may be a promising target of therapeutic strategies to control tumour growth.
- Źródło:
-
Acta Biochimica Polonica; 2005, 52, 2; 329-337
0001-527X - Pojawia się w:
- Acta Biochimica Polonica
- Dostawca treści:
- Biblioteka Nauki
Artykuł