TGF-beta 1 and TNF-alpha differentially regulate Twist1 mediated resistance towards BRAF/MEK inhibition in melanoma

Menon, Dinoop R., Wels, Christian, Rad, Ehsan Bonyadi, Joshi, Shripad, Knausz, Heike, Lade-Keller, Johanne, Brandner, Johanna M. and Schaider, Helmut (2013) TGF-beta 1 and TNF-alpha differentially regulate Twist1 mediated resistance towards BRAF/MEK inhibition in melanoma. Pigment Cell and Melanoma Research, 26 6: 912-916. doi:10.1111/pcmr.12139


Author Menon, Dinoop R.
Wels, Christian
Rad, Ehsan Bonyadi
Joshi, Shripad
Knausz, Heike
Lade-Keller, Johanne
Brandner, Johanna M.
Schaider, Helmut
Title TGF-beta 1 and TNF-alpha differentially regulate Twist1 mediated resistance towards BRAF/MEK inhibition in melanoma
Formatted title
TGF-b1 and TNF-a differentially regulate Twist1mediated resistance towards BRAF/MEK inhibition in melanoma
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
1755-148X
Publication date 2013-11-01
Sub-type Article (original research)
DOI 10.1111/pcmr.12139
Volume 26
Issue 6
Start page 912
End page 916
Total pages 6
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell
Language eng
Formatted 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.  
Keyword Twist1
Tgf-1
Tnf-
BRAF
Drug resistance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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