title: TGF-beta signaling in onset and progression of hepatocellular carcinoma
creator: Meindl-Beinker, Nadja M.
creator: Matsuzaki, Koichi
creator: Dooley, Steven
subject: ddc-610
subject: 610 Medical sciences Medicine
description: Transforming growth factor (TGF)-beta is a central regulator in chronic liver disease, contributing to all stages of disease progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver damage-induced levels of active TGF-beta enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Further evidence points to a decisive role of cytostatic and apoptotic functions mediated on hepatocytes, which is critical for the control of liver mass, with loss of TGF-beta activities resulting in hyperproliferative disorders and cancer. This concept is based on studies that describe a bipartite role of TGF-beta with tumor suppressor functions at early stages of liver damage and regeneration, whereas during cancer progression TGF-beta may turn from a tumor suppressor into a tumor promoter that exacerbates invasive and metastatic behavior. We have delineated this molecular switch of the pathway from cytostatic to tumor promoting in further detail and identify activation of survival signaling pathways in hepatocytes as a most critical requirement. Targeting the TGF-beta signaling pathway has been explored to inhibit liver disease progression. While interfering with TGF-beta signaling in various short-term animal models has demonstrated promising results, liver disease progression in humans is a process of decades with different phases in which TGF-beta or its targeting may have both beneficial and adverse outcomes.  We emphasize that, in order to achieve therapeutic  effects, targeting TGF-beta signaling in the right cell type at the right time is required. Copyright © 2012 S. Karger AG, Basel
publisher: S. Karger AG
date: 2012
type: Article
type: info:eu-repo/semantics/article
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/17791/1/DDI2012030005514.pdf
identifier: DOI:10.11588/heidok.00017791
identifier: urn:nbn:de:bsz:16-heidok-177916
identifier:   Meindl-Beinker, Nadja M. ; Matsuzaki, Koichi ; Dooley, Steven  (2012) TGF-beta signaling in onset and progression of hepatocellular carcinoma.  Digestive diseases, 30 (5).  pp. 514-523.  ISSN 0257-2753     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/17791/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng