Summary
This research project investigates the posttranslational regulation of macropinocytosis by PP2A-B56a in pancreatic cancer to identify novel therapeutic targets and enhance the efficacy of metabolic inhibitors.
Posttranslational regulation of macropinocytosis in pancreatic cancer
US · IL
NIH
grant
awarded
#nih-1R01CA295946-01A1
What they want
The project addresses the metabolic vulnerability of pancreatic ductal adenocarcinoma (PDAC) cells, which rely on glutamine but can circumvent this dependence through macropinocytosis. It hypothesizes that activating PP2A-B56a can sensitize PDAC tumors to glutamine antagonists by blocking macropinocytosis-dependent nutrient acquisition, thereby limiting metabolic plasticity. The research will explore the signaling mechanisms regulating macropinocytosis and its contribution to aggressive cancer phenotypes, specifically focusing on the role of PP2A-B56a, which has been shown to accelerate KRAS-driven pancreatic lesions when genetically lost.
Deliverables
- Identify the posttranslational mechanisms by which PP2A-B56a regulates macropinosome-lysosome fusion
- Evaluate the impact of PP2A activation on PDAC progression and macropinocytosis in vivo
- Determine if PP2A activation increases the efficacy of metabolic inhibitors, in vitro and in vivo
Technical requirements
- In vivo mouse model studies
- In vitro studies
