KAP-1 is overexpressed and correlates with increased metastatic ability and tumorigenicity in pancreatic cancer
- 468 Downloads
This study aimed to investigate the role in metastasis and prognostic value of KAP-1 in pancreatic cancer (PC). The expression of KAP-1 was analyzed by quantitative real-time polymerase chain reaction, Western blotting, and immunohistochemical staining in 91 human PC tissue samples. Capan-2 cells were transfected with a lentiviral vector expressing KAP-1 (Capan-2/KAP-1) or the empty vector (Capan-2/vector); cell migration and invasion were assayed in vitro using Transwell migration and wound-healing assays, and in vivo using a xenograft model in nude mice. KAP-1 was found to be overexpressed in human PC, and the expression of KAP-1 correlated with clinical stage. Overexpression of KAP-1 increased the invasion and migration of Capan-2 cells in vitro. Furthermore, overexpression of KAP-1 promoted the growth and metastatic ability of PC cells in a xenograft model in nude mice. Moreover, overexpression of KAP-1 induced the epithelial–mesenchymal transition (EMT) in PC cells both in vitro and in vivo, as indicated by increased expression of mesenchymal markers such as vimentin and decreased expression of E-cadherin. This study indicates that KAP-1 may promote metastasis in PC by regulating the EMT and suggests that KAP-1 may have potential as a predictor of metastasis in patients with pancreatic cancer.
KeywordsKAP-1 EMT Metastasis Tumorigenicity Pancreatic cancer
The authors thank the other members of the Professor Chengyi Sun and Renyi Qin’s laboratory for their help and technical support with this project. This study was supported by the National Natural Science Foundation of China (No. 81160311); and the International Science & Technology Cooperation Program of China (No. 2014DFA31420); and the Outstanding Young Training Project of Science and Education of Guizhou Province (No. 177).
Conflict of interest
We certify that regarding this paper, no actual or potential conflicts of interests exist; the work is original, has not been accepted for publication nor is concurrently under consideration elsewhere, and will not be published elsewhere without the permission of the Editor, and that all the authors have contributed directly to the planning, execution, or analysis of the work reported or to the writing of the paper.
- 2.Arslan AA, Helzlsouer KJ, Kooperberg C, Shu XO, Steplowski E, Bueno-de-Mesquita HB, Fuchs CS, Gross MD, Jacobs EJ, Lacroix AZ, Petersen GM, Stolzenberg-Solomon RZ, Zheng W, Albanes D, Amundadottir L, Bamlet WR, Barricarte A, Bingham SA, Boeing H, Boutron-Ruault MC, Buring JE, Chanock SJ, Clipp S, Gaziano JM, Giovannucci EL, Hankinson SE, Hartge P, Hoover RN, Hunter DJ, Hutchinson A, Jacobs KB, Kraft P, Lynch SM, Manjer J, Manson JE, McTiernan A, McWilliams RR, Mendelsohn JB, Michaud DS, Palli D, Rohan TE, Slimani N, Thomas G, Tjonneland A, Tobias GS, Trichopoulos D, Virtamo J, Wolpin BM, Yu K, Zeleniuch-Jacquotte A, Patel AV. Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan). Arch Intern Med. 2010;170:791–802.PubMedCentralPubMedCrossRefGoogle Scholar
- 8.Ryan RF, Schultz DC, Ayyanathan K, Singh PB, Friedman JR, Fredericks WJ, Rauscher FJ 3rd. KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for Kruppel-associated box-zinc finger proteins in heterochromatin-mediated gene silencing. Mol Cell Biol. 1999;19:4366–78.PubMedCentralPubMedGoogle Scholar
- 18.Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Choi W, Gerner EW, Ramdas L, Dupart J, Carew J, Proctor L, Huang P, Zhang W, Hamilton SR. Combination of 5-fluorouracil and N1, N11-diethylnorspermine markedly activates spermidine/spermine N1-acetyltransferase expression, depletes polyamines, and synergistically induces apoptosis in colon carcinoma cells. J Biol Chem. 2005;280:3295–304.PubMedCentralPubMedCrossRefGoogle Scholar