Nuclear Transcription Factors and Signaling Pathways in Oral Cancer Metastasis



Tumor progression of oral and other head and neck squamous cell carcinomas (HNSCCs) from dysplasia to metastasis involves a series of pathologic phenotypic changes considered to be the hallmarks of cancer, and these have been associated with a number of genetic, epigenetic, and molecular alterations (Fig. 10.1). Pathologic phenotypic changes precede metastasis and include increased cell proliferation, survival, and horizontal spread, which require certain molecular changes that together with later events contribute to the metastatic phenotype. These steps commonly include altered expression of molecules regulating the cell cycle and death (e.g., p53), growth factor response (epidermal growth factor receptor, EGFR), protein synthesis and metabolism (mammalian targets of rapamycin, mTOR), and cell immortality (telomerase). The subsequent steps of invasion and metastasis involve penetration and breakdown of the extracellular matrix (ECM) comprising the basement membrane and interstitial connective tissue; formation and invasion of a new stroma of host inflammatory and mesenchymal cells; neoangiogenesis and lymphangiogenesis; and distant spread via these lymphatics and blood vessels to secondary regional and distant sites. The molecular events accompanying the metastatic stage commonly include loss of expression or function of tumor suppressor genes or increased expression or function of oncogenes including numerous growth factors, cytokines, cell adhesion molecules and proteases, signal kinases, and nuclear transcription factors. Nuclear transcription factors appear to play a central role in malignant transformation and metastasis, since direct overexpression, mutation or activation of these molecules, or components of various upstream signaling pathways that modulate their function (Chaps. 8, 9, 11, 13) result in altered regulation of expression of diverse gene programs that produce the phenotypic changes characteristic of cancer and metastasis (Chaps. 4, 5, 12–14).


Vascular Endothelial Growth Factor Squamous Cell Carcinoma Nuclear Transcription Factor Squamous Cell Carcinoma Cell HNSCC Cell 



This work is supported by NIDCD Intramural project Z01-DC-000016, Z01-DC-000073 and Howard Hughes Medical Institute-NIH research scholarship (Reza Ehsanian). We would like to express our appreciation to Dr. Bin Yan for his effort in reference management.


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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Head and Neck Surgery BranchNational Institute on Deafness and Other Communication Disorders, National Institutes of HealthBethesdaUSA

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