Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Menon, DR; Wels, C; Bonyadi Rad, E; Joshi, S; Knausz, H; Lade-Keller, J; Brandner, JM; Schaider, H.
TGF-β1 and TNF-α differentially regulate Twist1 mediated resistance towards BRAF/MEK inhibition in melanoma.
Pigment Cell Melanoma Res. 2013; 26(6):912-916
Doi: 10.1111/pcmr.12139
Web of Science
PubMed
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FullText_MUG
- Führende Autor*innen der Med Uni Graz
- Schaider Helmut
- Co-Autor*innen der Med Uni Graz
- Bonyadirad Ehsan
- Joshi Shripad Prakash
- Knausz Heike
- Wels Christian
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- Abstract:
- Resistance to BRAF and MEK inhibition is a common phenomenon in melanoma. Cytokines and transcription factors have been attributed to contribute to the loss of sensitivity towards these inhibitors. Here, we show that transforming growth factor (TGF)-β1 if combined with PLX4032, a BRAF inhibitor, or GSK1120212, a MEK inhibitor, substantially increased cell death in BRAF-mutant melanoma cell lines. This increase was based on the combined regulatory decrease in Twist1, an antiapoptotic protein. Overexpression or silencing of Twist1 attenuated or aggravated induction of apoptosis through PLX4032 or GSK1120212, respectively. Exposure to tumour necrosis factor (TNF)-α, however, led to increased Twist1 levels and oppositional decrease in cell death if exposed to PLX4032 or GSK1120212. This increase in drug resistance again depended on Twist1 levels. Our studies suggest that Twist1 as a common downstream target of multiple signalling cascades plays a crucial role in mediating drug resistance to BRAF- and MEK-targeted molecular inhibitors. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
- Find related publications in this database (using NLM MeSH Indexing)
- Apoptosis - drug effects
- Caspase 3 - metabolism
- Cell Line, Tumor -
- Drug Resistance, Neoplasm - drug effects
- Humans -
- Indoles - pharmacology
- Melanoma - enzymology
- Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
- Nuclear Proteins - metabolism
- Proto-Oncogene Proteins B-raf - antagonists & inhibitors
- Pyridones - pharmacology
- Pyrimidinones - pharmacology
- Sulfonamides - pharmacology
- Transforming Growth Factor beta1 - pharmacology
- Tumor Necrosis Factor-alpha - pharmacology
- Twist Transcription Factor - metabolism
- Find related publications in this database (Keywords)
- Twist1
- TGF-1
- TNF-
- BRAF
- drug resistance