Palladin's Role in "TGF-?1" Induced EMT in Canine Renal Epithelial and Human Pancreatic Cancer Cells (2011)

Undergraduates: Samuel Glaubiger, Judy Staub

Faculty Advisor: Carol Otey
Department: Biology

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The aim of my project was to investigate epithelial-to-mesenchymal transition (EMT), a process whereby cuboidal-shaped epithelial cells lose their cell-cell adhesions, acquire a spindle shape, and become more motile. EMT is important in both physiology and pathology, as it contributes to embryonic development, wound-healing, fibrosis and cancer metastasis; however, the precise molecular mechanisms that underlie EMT are poorly understood. I focused on palladin, an actin-associated protein that has been shown to play a critical role in organizing the cytoskeleton. Previous studies have shown that the 90 kD and 140 kD palladin isoforms are expressed in mesenchymal cells and not detected in epithelial cells. I set out to test the hypothesis that isoform-specific palladin upregulation may lead to the acquisition of a mesenchymal phenotype. To test this hypothesis, I utilized MDCK kidney epithelial cells to model fibrosis, and Panc-1 pancreatic tumor cells to model cancer metastasis. To induce EMT, I treated both types of cells with the cytokine TGF-β1, and then performed western blot analysis to detect palladin. The results showed that a 140 kD isoform of palladin was upregulated in both samples. In addition, Panc-1 cells showed a subsequent increase in a 90 kD isoform. Therefore, these results suggest that isoform-specific upregulation of palladin may contribute to the development of fibrosis and also to the increased invasiveness and metastatic potential of solid tumors.