Document Detail


Stat3 - Linking inflammation to (gastrointestinal) tumourigenesis.
MedLine Citation:
PMID:  22211709     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Tumourigenesis is a multistage process comprising initiation, promotion and progression that is governed by cumulative (epi-)genetic changes. However, tumour initiation, triggered by mutations in proto-oncogenes and/or tumour suppressor genes, is insufficient for the development of cancers. Tumour promotion often depends on the interaction between initiated cells and the microenvironment where excessive abundance of inflammatory mediators, including those of the interleukin (IL-)6/gp130 family, promote their expansion. The activity of most soluble mediators ultimately converge on tumour cells through activation of the latent transcription factors NF-κB and Stat3 to enhance survival of neoplastic cells. In addition, Stat3 also promotes tumour cell proliferation, invasion and induction of an angiogenic switch. Persistent activation of STAT3 is a unifying hallmark of a majority of solid malignancies. However, persistent STAT3 activation occurs usually in the absence of activating mutations in, or amplification of, the STAT3 gene. Instead, it is associated with an oversupply of autocrine and/or paracrine activating cytokines secreted by tumour and stromal cells and comprising (among others) cytokines that utilize the gp130 receptor. IL6, IL11 and other members of the gp130 cytokine family have been identified in preclinical mouse models as promising therapeutic targets for gastrointestinal, hepatic and breast cancers. Thus, pharmacological interference with specific cytokines and tyrosine kinases that trigger Stat3 activation affords opportunities to therapeutically target the non-redundant tumour promoting signalling function of Stat3. © 2011 The Authors Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
Authors:
Matthias Ernst; Tracy L Putoczki
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-28
Journal Detail:
Title:  Clinical and experimental pharmacology & physiology     Volume:  -     ISSN:  1440-1681     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0425076     Medline TA:  Clin Exp Pharmacol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 The Authors Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.
Affiliation:
Ludwig Institute for Cancer Research, Melbourne Parkville Branch, AUSTRALIA.
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