Cargando…
PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma
Background: In cancer biology, metastasizing is one of the most poorly studied processes. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastasis, which is the leading cause of death. The PDX1 protein is crucial for the development of cancer, and its low levels are characteristi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666369/ https://www.ncbi.nlm.nih.gov/pubmed/31440095 http://dx.doi.org/10.2147/CMAR.S209940 |
_version_ | 1783439978769940480 |
---|---|
author | Kondratyeva, Liya G Safina, Dina R Chernov, Igor P Kopantzev, Eugene P Kostrov, Sergey V Sverdlov, Eugene D |
author_facet | Kondratyeva, Liya G Safina, Dina R Chernov, Igor P Kopantzev, Eugene P Kostrov, Sergey V Sverdlov, Eugene D |
author_sort | Kondratyeva, Liya G |
collection | PubMed |
description | Background: In cancer biology, metastasizing is one of the most poorly studied processes. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastasis, which is the leading cause of death. The PDX1 protein is crucial for the development of cancer, and its low levels are characteristic of the most aggressive PDAC tumors. The PDX1 is a mediator of initiation and progression of PDAC. However, further studies are needed to elucidate the role of PDX1 in the cancer metastasis. Purpose: To confirm the hypothesis that PDX1 in PDAC plays suppressor role of epithelial–mesenchymal transition (EMT), and to study its possible ability to inhibit metastasis. Methods: A PDX1-overexpressing PDAC cell line was obtained by lentiviral transduction of PANC-1 cells. PDX1 overexpression was confirmed by RT-PCR and Western blotting. Effects of PDX1 ectopic expression on cell proliferation and motility were determined in PANC-1 cells using MTS, cell cycle analysis, transwell and wound-healing assay. EMT genes expression was analyzed in PDX1-overexpressing and Control PANC-1. Finally, the migration potential of pancreatic cancer cells expressing PDX1 was evaluated using a zebrafish embryo model. Results: The motility of human PDAC cells PANC-1 considerably decreased at ectopic expression of PDX1. The decreased expression of ZEB1, the key factor of EMT, and almost unchanged expression of the genes that characterize the epithelial state suggest a decrease in the EMT ability. Suppression of PDX1 expression by siRNA knockdown restored the PANC1 motility. Conclusion: The results obtained suggest a possible therapeutic use of PDX1 delivery into PDAC patients with a reduced or absent expression of PDX1 in the most aggressive tumors. |
format | Online Article Text |
id | pubmed-6666369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-66663692019-08-22 PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma Kondratyeva, Liya G Safina, Dina R Chernov, Igor P Kopantzev, Eugene P Kostrov, Sergey V Sverdlov, Eugene D Cancer Manag Res Original Research Background: In cancer biology, metastasizing is one of the most poorly studied processes. Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastasis, which is the leading cause of death. The PDX1 protein is crucial for the development of cancer, and its low levels are characteristic of the most aggressive PDAC tumors. The PDX1 is a mediator of initiation and progression of PDAC. However, further studies are needed to elucidate the role of PDX1 in the cancer metastasis. Purpose: To confirm the hypothesis that PDX1 in PDAC plays suppressor role of epithelial–mesenchymal transition (EMT), and to study its possible ability to inhibit metastasis. Methods: A PDX1-overexpressing PDAC cell line was obtained by lentiviral transduction of PANC-1 cells. PDX1 overexpression was confirmed by RT-PCR and Western blotting. Effects of PDX1 ectopic expression on cell proliferation and motility were determined in PANC-1 cells using MTS, cell cycle analysis, transwell and wound-healing assay. EMT genes expression was analyzed in PDX1-overexpressing and Control PANC-1. Finally, the migration potential of pancreatic cancer cells expressing PDX1 was evaluated using a zebrafish embryo model. Results: The motility of human PDAC cells PANC-1 considerably decreased at ectopic expression of PDX1. The decreased expression of ZEB1, the key factor of EMT, and almost unchanged expression of the genes that characterize the epithelial state suggest a decrease in the EMT ability. Suppression of PDX1 expression by siRNA knockdown restored the PANC1 motility. Conclusion: The results obtained suggest a possible therapeutic use of PDX1 delivery into PDAC patients with a reduced or absent expression of PDX1 in the most aggressive tumors. Dove 2019-07-26 /pmc/articles/PMC6666369/ /pubmed/31440095 http://dx.doi.org/10.2147/CMAR.S209940 Text en © 2019 Kondratyeva et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Kondratyeva, Liya G Safina, Dina R Chernov, Igor P Kopantzev, Eugene P Kostrov, Sergey V Sverdlov, Eugene D PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title | PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title_full | PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title_fullStr | PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title_full_unstemmed | PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title_short | PDX1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
title_sort | pdx1, a key factor in pancreatic embryogenesis, can exhibit antimetastatic activity in pancreatic ductal adenocarcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6666369/ https://www.ncbi.nlm.nih.gov/pubmed/31440095 http://dx.doi.org/10.2147/CMAR.S209940 |
work_keys_str_mv | AT kondratyevaliyag pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma AT safinadinar pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma AT chernovigorp pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma AT kopantzeveugenep pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma AT kostrovsergeyv pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma AT sverdloveugened pdx1akeyfactorinpancreaticembryogenesiscanexhibitantimetastaticactivityinpancreaticductaladenocarcinoma |