Osteopontin (OPN) is a critical signaling molecule that regulates downstream Twist in human salivary gland (SG) cancers. Fos-realated Antigen-1 (Fra-1) is a protein that plays an important role in regulating mechanisms, like those that determine cell shape, which can lead to SG cancer cell migration and metastasis. Twist regulates cell morphology by driving cells through a process known as epithelial-mesenchymal transition (EMT). EMT is an important change needed during embryonic development, but in the adult can often lead to pathology. Although our lab has previously established independent roles of OPN and Twist in cell migration and changes in cell morphology, possible interconnections between OPN, Fra-, and Twist have not been studied in depth. I examined the potential upstream regulation of Fra-1 and Twist by OPN through the Mitogen Activated Protein Kinase/Extracellular Signal-Related Kinase (MAPK/ERK) pathway. I used immunofluorescence studies to localize and quantify the components of the MAPK/ERK pathway in non-cancerous and cancerous SG cell lines. I further modulated the pathways in these cell lines using ERK1/2 activators and inhibitors. Finally, I silenced OPN via siRNA silencing techniques to conclusively evaluate the role of OPN in regulating Fra-1 and Twist. I found evidence that OPN could be an important regulator of MAPK/ERK pathway, which includes downstream Fra-1 and Twist.
|Commitee:||DiSalvo, Susanne, Kohn, Luci, Liebl, Faith|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 58/06M(E), Masters Abstracts International|
|Keywords:||Cancer, Fra-1, Osteopontin, Salivary glands, Twist|
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