Dysregulated molecular networks in head and neck carcinogenesis.
Multiple genetic and epigenetic events, including the aberrant expression and function of molecules regulating cell signaling, growth, survival, motility, angiogenesis, and cell cycle control, underlie the progressive acquisition of a malignant phenotype in squamous carcinomas of the head and neck (HNSCC). In this regard, there has been a recent explosion in our understanding on how extracellular components, cell surface molecules, and a myriad of intracellular proteins and second messenger systems interact with each other, and are organized in pathways and networks to control cellular and tissue functions and cell fate decisions. This emerging ability to understand the basic mechanism controlling inter- and intra-cellular communication has provided an unprecedented opportunity to understand how their dysregulation contributes to the growth and dissemination of human cancers. Here, we will discuss the emerging information on how the use of modern technologies, including gene array and proteomic studies, combined with the molecular dissection of aberrant signaling networks, including the EGFR, ras, NFkappaB, Stat, Wnt/beta-catenin, TGF-beta, and PI3K-AKT-mTOR signaling pathways, can help elucidate the molecular mechanisms underlying HNSCC progression. Ultimately, we can envision that this knowledge may provide tremendous opportunities for the diagnosis of premalignant squamous lesions, and for the development of novel molecular-targeted strategies for the prevention and treatment of HNSCC.
Molinolo
Alfredo A
AA
Oral and Pharyngeal Cancer Branch, National Institute of Craniofacial and Dental Research, National Institutes of Health, Building 30, Room 211, 30 Convent Drive, Bethesda, MD 20892-4330, USA.
Amornphimoltham
Panomwat
P
Squarize
Cristiane H
CH
Castilho
Rogerio M
RM
Patel
Vyomesh
V
Gutkind
J Silvio
JS
D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009857:Oncogenes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011230:Precancerous Conditions / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors