UNIGE document Doctoral Thesis
previous document  unige:37048  next document
add to browser collection
Title

Targeting STAT3 for cancer therapy: definition of mechanisms of action of direct STAT3 inhibitors

Author
Directors
Catapano, Carlo
Defense Thèse de doctorat : Univ. Genève, 2013 - Sc. 4598 - 2013/10/10
Abstract STAT3 is a cytoplasmic transcription factor that, once activated, conveys extracellular signals to the nucleus. Activation is achieved through Tyr705 phosphorylation that induces dimerization, nuclear translocation and transcriptional activation of target genes. STAT3 can also be phosphorylated on Ser727. Moreover, its hyper-activation has been implicated in several human cancers. Therefore, STAT3 is a good target candidate for development of anticancer drugs. STAT3 inhibitors are usually divided into indirect inhibitors, acting on upstream pathways, and direct inhibitors, directly binding to STAT3. The aim of this work was to investigate the mechanisms of action of different direct STAT3 inhibitors and define a common mode of action. All compounds showed a reduction of pTyr705 and pSer727 as well as an inhibition of proliferation and clonogenicity of cancer cells, although at different concentrations. These results were consistent with a direct binding of the drugs to STAT3-SH2 domain, confirmed by computational models and site-directed mutagenesis.
Identifiers
URN: urn:nbn:ch:unige-370482
Full text
Thesis (4.7 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Citation
(ISO format)
BRAMBILLA, Lara. Targeting STAT3 for cancer therapy: definition of mechanisms of action of direct STAT3 inhibitors. Université de Genève. Thèse, 2013. https://archive-ouverte.unige.ch/unige:37048

323 hits

1 download

Update

Deposited on : 2014-06-02

Export document
Format :
Citation style :