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PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration
Helen King1, Kiruthikah Thillai1, Andrew Whale1
1Division of Cancer Studies, King's College London, UK.
Scientific Reports
|February 17, 2017
Summary
p21-activated kinase 4 (PAK4) is elevated in pancreatic cancer, interacting with the PI3K pathway. This interaction is crucial for HGF-induced cell motility, suggesting PAK4 as a therapeutic target for pancreatic ductal adenocarcinoma (PDAC).
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer.
- PAK4 functions downstream of HGF-mediated c-Met activation in a PI3K-dependent manner.
- The role of PAK4 and HGF signaling in pancreatic cancer cell motility requires further investigation.
Purpose of the Study:
- To investigate the functionality of PAK4 in pancreatic cancer.
- To elucidate the contribution of HGF signaling to pancreatic cancer cell motility.
- To explore the interaction between PAK4 and the PI3K pathway.
Main Methods:
- Analysis of PAK4, c-Met, and PI3K p85α subunit expression in pancreatic cancer cells.
- Assessment of pancreatic cancer cell motility in response to HGF using 2D and 3D organotypic assays.
- Investigation of the interaction between PAK4 and p85α, and the effect of PAK4 deficiency on Akt phosphorylation.
Main Results:
- Elevated PAK4 expression correlates with increased c-Met and PI3K p85α levels.
- Pancreatic cancer cells exhibit HGF-induced motility, suppressible by PI3K inhibition.
- A specific interaction between PAK4 and p85α was identified, with PAK4 deficiency reducing HGF-induced Akt phosphorylation.
Conclusions:
- PAK4 plays a novel role in the PI3K pathway through interaction with p85α.
- PAK4 is implicated in pancreatic ductal adenocarcinoma (PDAC) progression.
- PAK4 represents a potential therapeutic target for pancreatic cancer.
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