Alterations of Transforming Growth Factor-β Signaling in Squamous Cell Carcinomas



Genetic mouse models have clearly demonstrated that either activation or attenuation of the transforming growth factor-(TGF-)β and the TGF-β signaling pathway can have a major impact on either the genesis and/or the progression of squamous cell carcinomas (SCC) in the epidermis as well as in the head-and-neck region. In general, inactivation of the TGF-β signaling pathway in stratified squamous epithelium promotes the de novo emergence of benign papillomas that have the potential to progress to invasive SCC. On the other hand, activation of TGF-β signaling in established SCC clearly favors their progression to highly invasive and metastatic SCC. Furthermore, a large number of reports of structural and functional alterations in TGF-β pathway components in human SCC cell lines as well as tumor specimens strongly support the idea that this pathway in general, and TGF-β receptors in particular, play an important role in human SCC as well. Attenuation of either Type I TGF-β receptor (TβR)-I or -II signaling promotes SCC development in mice, and mutation and/or loss of expression of TβR-I or -II receptors are commonly seen in human SCC. Thus, approximately 10–15% of head and neck squamous cell carcinoma (HNSCC) display evidence of functional inactivation of TβR receptor signaling, as defined by the absence of pSmad2 and -3 or the presence of an inactivating TGFBR gene mutation. Patients with this tumor type appear to have a particularly favorable clinical outcome. On the other hand, in approximately 40–60% of human SCC TβR expression is reduced but not eliminated. In this context, exposure of the tumor cells to bioactive TGF-β will activate a proinvasive and -metastatic gene expression program, thereby conferring a worse clinical outcome. Therefore, we would like to propose that a structural and functional analysis of the TβR receptors potentially represents a powerful prognostic tool for the management of patients with SCC.


Squamous Cell Carcinoma Esophageal Squamous Cell Carcinoma Invasive Squamous Cell Carcinoma Cervical Squamous Cell Carcinoma Squamous Cell Carcinoma Cell Line 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





Extracellular matrix


Epithelial-to-mesenchymal transition


Human head-and-neck squamous cell carcinoma(s)




Matrix metalloproteinase


Squamous cell carcinoma(s)


Single-strand conformation polymorphism

TGFBR1, Tgfbr-1

Type I TGF-β receptor gene

TGFBR2, Tgfbr-2

Type II TGF-β receptor gene


Transforming growth factor-β




Type I TGF-β receptor


Type II TGF-β receptor


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Medical Oncology, Department of Internal Medicine, The Cancer Institute of New JerseyUMDNJ-Robert Wood Johnson Medical SchoolNew BrunswickUSA

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