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CPA4 Promotes EMT in Pancreatic Cancer via Stimulating PI3K-AKT-mTOR Signaling
- Source :
- OncoTargets and Therapy, Vol Volume 13, Pp 8567-8580 (2020)
- Publication Year :
- 2020
- Publisher :
- Dove Medical Press, 2020.
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Abstract
- Qingliang Shao,1 Zhiqiang Zhang,1 Rongxian Cao,2 Hui Zang,1 Wanting Pei,2 Tian Sun2 1Department of General Surgery, The Peoples’ Hospital of Liaoning Province, Shenyang City, Liaoning Province, People’s Republic of China; 2Graduate School of China Medical University, Shenyang City, Liaoning Province, People’s Republic of ChinaCorrespondence: Hui Zang Email Drzanghui0320@163.comBackground: 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.Keywords: CPA4, EMT, pancreatic cancer, PI3K-AKT-mTOR signaling
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- ume 13
- Database :
- Directory of Open Access Journals
- Journal :
- OncoTargets and Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2444b2cf4651474892ed776e81fb787e
- Document Type :
- article