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Presentation date

Summer 8-12-2021

Faculty Mentor

Dr. Moorthy P. Ponnusamy

Research Mentor

Dr. Moorthy P. Ponnusamy

Abstract

Pancreatic cancer is a highly aggressive human cancer and the third leading cause of death due to cancer. Cancer stems cells (CSC) are a small population of cancer cells that mediate tumorigenesis, metastasis, and resistance to standard treatments. By specifically identifying and targeting CSC maintenance genes, the efficiency of treatment modalities can be improved. PAF1 (RNA Polymerase II-Associated Factor 1), also known as PD2 (Pancreatic Differentiation 2) maintains pluripotency of stem cells and is a marker of pancreatic cancer stem cells. It is upregulated in poorly differentiated pancreatic cancer cells. Gemcitabine is a novel deoxycytidine analogue which has been developed as an anticancer therapy. It is widely used as a chemotherapeutic agent and is presently the most effective agent against pancreatic cancer.

Our project aimed at understanding the role of PAF1/PD2 in the maintenance of pancreatic cancer stem cells and its contribution to gemcitabine resistance. Immunohistochemistry and Bioinformatics analysis showed increased PAF1 expression in PDAC tumor samples. Through various experimental methods, it was shown that gemcitabine increases the expression of PAF1/PD2 and CSC markers and that the loss of PAF1/PD2 influences the maintenance of PC cells and sensitizes the cells to gemcitabine. The impact of PAF1/PD2 on gemcitabine resistance and CSC marker expression and on human pancreatic tumor samples was also studied.

It was concluded that PAF1/PD2 are overexpressed in pancreatic tumor cells, increased expression of PAF1/PD2 is associated with gemcitabine resistance in pancreatic cancer cells, the knockdown of PAF1/PD2 leads to a significant reduction in expression of CSC markers and pancreatic tumorigenesis, and human pancreatic tumor samples showed increased expression of PAF1/PD2. Additionally, altered expression of PAF1/PD2 has prognostic relevance to pancreatic cancer patient survival.

Keywords

Pancreatic cancer, cancer stem cells, gemcitabine, PAF1, drug resistance

The Role of PAF1/PD2 in Inducing Drug Resistance In Pancreatic Cancer Cells
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