Transforming Growth Factor Beta (TGF-β) Signaling in Head and Neck Squamous Cell Carcinoma (HNSCC)

  • Alexander E. Kudinov
  • Tim N. BeckEmail author
Part of the Current Cancer Research book series (CUCR)


Transforming growth factor receptor beta (TGF-β) signaling is commonly dysregulated in head and neck squamous cell carcinoma (HNSCC). TGF-β signaling influences homeostasis in normal epithelial cells and regulates a critical signaling network during development. In HNSCC, TGF-β signaling frequently promotes cell invasion, metastasis, proliferation, and drug resistance and may present an important therapeutic target. Canonical TGF-β signaling generally involves activation of SMAD effector proteins, most prominently SMAD2 and SMAD3, whereas noncanonical TGF-β signaling requires signal propagators including ERK, AKT, and RAF, also commonly employed by receptor tyrosine kinases (RTKs), thereby providing opportunities for signaling crosstalk. Several members of the TGF-β superfamily are being explored as potential targets to control drug resistance and metastatic spread, both important barriers to cure in HNSCC. In this chapter, the roles of TGF-β in HNSCC are described, with particular focus on molecular signaling, TGF-β’s role in controlling gene expression, and relevant therapeutic directions involving TGF-β.


TGF-β TGFBRII Head and neck cancer Targeted therapy Metastasis Proliferation Epithelial-mesenchymal transition Cancer stem cells 



We thank Drs. Golemis and Burtness for critical reading of our chapter. The authors were supported by the Ruth L. Kirschstein NRSA F30 fellowship (F30 CA180607) from the NIH (to TNB).


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular Therapeutics Program, Fox Chase Cancer CenterPhiladelphiaUSA
  2. 2.Department of Internal Medicine, University of New MexicoAlbuquerqueUSA
  3. 3.Program in Molecular and Cell Biology and Genetics, Drexel University College of MedicinePhiladelphiaUSA

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