The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models

TGFβ1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have a potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and in...

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Main Author: Adam B. Glick
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Journal of Skin Cancer
Online Access:http://dx.doi.org/10.1155/2012/249063
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author Adam B. Glick
author_facet Adam B. Glick
author_sort Adam B. Glick
collection DOAJ
description TGFβ1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have a potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and inflammation. TGFβ signaling is tightly regulated in normal tissues and becomes deregulated during cancer development in cutaneous SCC and many other solid tumors. Because of these diverse biological processes regulated by TGFβ1, this cytokine and its signaling pathway appear to function at multiple points during carcinogenesis with distinct effects. The mouse skin carcinogenesis model has been a useful tool to dissect the function of this pathway in cancer pathogenesis, with transgenic and null mice as well as small molecule inhibitors to alter the function of the TGFβ1 pathway and assess the effects on cancer development. This paper will review data on changes in TGFβ1 signaling in human SCC primarily HNSCC and cutaneous SCC and different mouse models that have been generated to investigate the relevance of these changes to cancer. A better understanding of the mechanisms underlying the duality of TGFβ1 action in carcinogenesis will inform potential use of this signaling pathway for targeted therapies.
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spelling doaj-art-27f2741126704ef2bd3b67ccfb033c392025-02-03T05:59:22ZengWileyJournal of Skin Cancer2090-29052090-29132012-01-01201210.1155/2012/249063249063The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse ModelsAdam B. Glick0Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USATGFβ1 is a member of a large growth factor family including activins/inhibins and bone morphogenic proteins (BMPs) that have a potent growth regulatory and immunomodulatory functions in normal skin homeostasis, regulation of epidermal stem cells, extracellular matrix production, angiogenesis, and inflammation. TGFβ signaling is tightly regulated in normal tissues and becomes deregulated during cancer development in cutaneous SCC and many other solid tumors. Because of these diverse biological processes regulated by TGFβ1, this cytokine and its signaling pathway appear to function at multiple points during carcinogenesis with distinct effects. The mouse skin carcinogenesis model has been a useful tool to dissect the function of this pathway in cancer pathogenesis, with transgenic and null mice as well as small molecule inhibitors to alter the function of the TGFβ1 pathway and assess the effects on cancer development. This paper will review data on changes in TGFβ1 signaling in human SCC primarily HNSCC and cutaneous SCC and different mouse models that have been generated to investigate the relevance of these changes to cancer. A better understanding of the mechanisms underlying the duality of TGFβ1 action in carcinogenesis will inform potential use of this signaling pathway for targeted therapies.http://dx.doi.org/10.1155/2012/249063
spellingShingle Adam B. Glick
The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
Journal of Skin Cancer
title The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
title_full The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
title_fullStr The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
title_full_unstemmed The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
title_short The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
title_sort role of tgfβ signaling in squamous cell cancer lessons from mouse models
url http://dx.doi.org/10.1155/2012/249063
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