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“PP2A as a regulator of pancreatic cancer cellular and metabolic plasticity”
Dr. Brittany Allen-Petersen
Assistant Professor of Biological Sciences Purdue University
Pancreatic cancer is predicted to become the 2nd leading cause of cancer deaths by 2030. KRAS is the most frequently mutated gene in pancreatic ductal adenocarcinoma (PDAC) patients (~90%) and has been shown to contribute to a variety of tumor characteristics. Protein phosphatases provide an essential “off switch” to oncogenic signaling pathways and are commonly dysregulated in cancer. In this presentation we will present data implicating Protein phosphatase 2A (PP2A) as a key regulator of KRAS-driven phenotypes during PDAC progression. Utilizing genetically engineered mouse models and 3D culture, we demonstrate that suppression of PP2A accelerates PDAC initiation and progression. Further, the acute therapeutic activation of PP2A deregulates macropinocytosis, a critical nutrient scavenging pathway, leading to PDAC cancer cell death.