HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway via stimulating MSK1 kinase and suppressing PPP2R2B protein

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective therapies. We demonstrated that the transcription factor, HOXC6, was overexpressed in most PDACs, and its inhibition blocked PDAC tumor growth and metastasis. HOXC6 transcriptionally activated the tumor-promoting kinase MSK1. To identify the phosphorylation targets of MSK1 and the mediators of its function in PANC1 cells, we utilized an unbiased TMT10-based phosphoproteomics analysis. To do so, we treated AsPC1 cells with MSK1 inhibitor SB-747651A and performed TMT10-based quantitative phosphoproteomics analysis and identified MSK1 phosphorylation targets.