Dataset Information
CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling.
Ontology highlight
ABSTRACT: Background
Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified.Materials and methods
We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro.Results
CPA4 was overexpressed in clinical PC samples that was positively related with tumor size (P=0.026), T stage (P=0.011), lymph-node metastasis (P=0.026) and a worse prognosis for PC patients (P=0.001). Interestingly, CPA4 was inversely correlated with E-cadherin (r=-0.372, P=0.003) in clinical samples and PC cell lines which cooperatively contributed to a worse prognosis (P=0.005) for PC patients. CPA4 overexpression enhanced EMT in AsPC-1 and Capan-2 cells, which promoted EMT-like cellular morphology and cell invasion and migration. Meanwhile, CPA4 overexpression activated EMT and PI3K-AKT-mTOR signaling, following with the downregulation of E-cadherin and β-catenin, and the upregulation of N-cadherin, vimentin, p-PI3K (Tyr458), p-AKT (Ser473) and p-mTOR (Ser2448). However, PI3K inhibitor LY294002 reversed CPA4 overexpression-stimulated EMT in vitro. Moreover, CPA4 was co-immunoprecipitated with AKT in two PC cells with CPA4 high expression. Conversely, CPA4 silencing inhibited EMT in PANC-1 cells. CPA4 overexpression or silencing promoted or inhibited cell proliferation and drug resistance in Capan-2 and PANC-1 cells via regulating Bcl2/Bax and cleaved-caspase3 signaling. However, LY294002 reversed CPA4 overexpression-stimulated cell proliferation and drug resistance in vitro in Bcl2/Bax and caspase3-dependent apoptosis.Conclusion
CPA4 overexpression contributes to aggressive clinical stage of PC patients and promotes EMT in vitro via activation of PI3K-AKT-mTOR signaling.
SUBMITTER: Shao Q
PROVIDER: S-EPMC7457871 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling.
OncoTargets and therapy 20200825
<h4>Background</h4>Carboxypeptidase A4 (CPA4), as a novel tumor biomarker, is prevalently observed in various cancers. However, the potential role of CPA4 in pancreatic cancer (PC), to our knowledge, has not been fully clarified.<h4>Materials and methods</h4>We systematically explored the detailed function of CPA4 in epithelial to mesenchymal transition (EMT) stimulated PC in human clinical samples and in vitro.<h4>Results</h4>CPA4 was overexpressed in clinical PC samples that was positively rel ...[more]