Phosphatidylserine Externalization in Pancreatic Cancer Cells is Associated with Increased Oxidative Stress, Actin Rearrangement and p38 Activation

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Priyankaben Patel
Xiaoyang Qi

Abstract

By Priyankaben Patel, Biological Sciences


Advisor: Xiaoyang Qi


Abstract: Background: Pancreatic cancer is the fourth leading cause of cancer deaths with a five-year survival rate of 9%. Pancreatic ductal adenocarcinoma (PDAC) accounting for about 90% of pancreatic tumors. Understanding the mechanisms that regulate PDAC proliferation will reveal novel therapeutic strategies to improve patient outcomes. Phosphatidylserine (PS) is a lipid biomarker typically found in the inner leaflet of healthy cells but in cancer cells, it is externalized by Ca2+ and decreased flippase activity. Importantly, PS externalization is associated with metastasis and poor treatment efficacy. Oxidative stress (OS) and reactive oxygen species (ROS) generation is a hallmark of the tumor microenvironment and is involved in cancer progression. OS is involved in regulating intracellular Ca2+ levels through ROS, actin rearrangement and p38-MAPK activation. We, therefore, hypothesized that OS in PDAC cells induces PS externalization through Ca2+ regulation and flippase inactivation. Methods: We utilized: (1) Hydrogen peroxide treatment to induce OS in PDAC cells, (2) Fluorescence microscopy and western blot to assess actin and p38-MAPK activation (3) Flow cytometry to measure surface PS, F-actin, Ca2+ and flippase after OS and p39-MAPK inhibition. Results: Our data show that OS leads to an increase in PS externalization, F-actin, and p38-MAPK activation and that stabilizing F-actin increases PS externalization. Furthermore, when OS was induced in cells in the presence of a p38-MAPK inhibitor, PS externalization remains unchanged. Conclusion: Our data suggest that OS is an important mechanism regulating PS externalization in PDAC cells and that inhibiting this pathway could decrease surface PS-related cancer-promoting effects.

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Classic Poster (9:45-11:45 AM)