Background
Overexpressed PES1 promotes carcinogenesis in various types of malignant tumors. However, the biological role and clinical significance of PES1 in pancreatic cancer are still unexplored.
Conclusions
We have shown that PES1 could be one of the promoting factors of tumor growth and a prognosis-related protein of pancreatic cancer. Targeting PES1 with CDK5 inhibitors might help overcome cancer cell resistance to BET inhibitors in pancreatic cancer cells.
Methods
The expression level of PES1 in pancreatic cancer cell lines and pancreatic cancer patient samples was determined using Western Blotting analysis, RT-qPCR analysis, immunohistochemical (IHC) analysis of tissue microarray, and the GEPIA web tool. MTS assay, colony formation assay, and xenograft tumor assay were used to evaluate the tumor growth ability of pancreatic cancer cells.
Results
We established that the expression of PES1 was abnormally increased in pancreatic cancer tissues and led to poor prognosis of pancreatic cancer patients. We also found that PES1 was responsible for promoting cell growth and contributed to bromodomain and cancer cell resistance to extra-terminal (BET) inhibitors in pancreatic cancer. Furthermore, we showed that PES1 interacted with BRD4 to enhance c-Myc expression, which is the primary cause of cancer cell resistance to BET inhibitors in pancreatic cancer. Finally, CDK5 inhibitors were proven to destabilize PES1 and overcome cancer cell resistance to BET inhibitors in pancreatic cancer cells. Conclusions: We have shown that PES1 could be one of the promoting factors of tumor growth and a prognosis-related protein of pancreatic cancer. Targeting PES1 with CDK5 inhibitors might help overcome cancer cell resistance to BET inhibitors in pancreatic cancer cells.