Electronic Thesis and Dissertation Repository


Master of Science


Physiology and Pharmacology


Di Guglielmo, John


Metastasis is responsible for 90% of cancer-related deaths. An important early step in the metastatic process is epithelial-to-mesenchymal transition (EMT) of tumor cells. Stimulated by TGFβ signaling, cells that undergo EMT have increased migratory and invasive potential, resulting in metastasis and the development of tumors at a secondary site. The TGFβ type 3 receptor (TβR3) has been implicated in modulating TGFβ signaling, yet its functional outcomes remain unclear. My findings demonstrated that TβR3 silencing does not alter TGFβ-dependent Smad2 phosphorylation in neither H1299, not A549 nonsmall cell lung carcinoma cells but reduces Smad2 expression in H1299 cells. Interestingly, although TβR3 knockdown did not alter mRNA expression of EMT markers, it resulted in the reduction of TGFβ-dependent EMT protein markers. Finally, inhibition of EMT attenuated cellular invasion while enhancing chemotactic migration. Together, these results suggest that TβR3 has a distinct role in modulating EMT and cellular motility in a Smad-independent manner.