| First Author | Cao XY | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 499 |
| Issue | 3 | Pages | 584-593 |
| PubMed ID | 29621546 | Mgi Jnum | J:271449 |
| Mgi Id | MGI:6280266 | Doi | 10.1016/j.bbrc.2018.03.194 |
| Citation | Cao XY, et al. (2018) Aberrant upregulation of KLK10 promotes metastasis via enhancement of EMT and FAK/SRC/ERK axis in PDAC. Biochem Biophys Res Commun 499(3):584-593 |
| abstractText | Pancreatic Ductal Adenocarcinoma (PADC) metastasis is the leading cause of morality of this severe malignant tumor. Proteases are key players in the degradation of extracellular matrix which promotes the cascade of tumor metastasis. As a kind of serine proteases, the kallikrein family performs vital function on the cancer proteolysis scene, which have been proved in diverse malignant tumors. However, the specific member of kallikrein family and its function in PDAC remain unexplored. In this study, by data mining of GEO datasets, we have identified KLK10 is upregulated gene in PDAC. We found that KLK10 was significantly overexpressed in tissues of pancreatic intraepithelial neoplasia (PanIN) and PDAC from Pdx1-Cre; LSL-Kras(G12D/+) mice (KC) and Pdx1-Cre; LSL-Kras(G12D/+); LSL-Trp53(R172H/+) mice (KPC) by immunohistochemical analysis. Moreover, KLK10 is extremely elevated in the PDAC tissues, especially that from the PDAC patients with lymphatic and distant metastasis. Aberrant KLK10 expression is significantly correlated with poor prognosis and shorter survival by univariable and multivariable analysis. Functionally, knockdown of KLK10 observably inhibits invasion and metastatic phenotype of PDAC cells in vitro and metastasis in vivo. In addition, blockade of KLK10 attenuates epithelial-mesenchymal transition and activation of FAK-SRC-ERK signaling, which explains the mechanism of KLK10 in promoting metastasis. Collectively, KLK10 should be considered as a promising biomarker for diagnosis and potential target for therapy in PDAC. |
