Cargando…

Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling

Slug, a member of the Snail family of transcription factors, has a crucial role in the regulation of epithelial-mesenchymal transition (EMT) by suppressing several epithelial markers and adhesion molecules, including E-cadherin. A recent study demonstrated that no relationship exists between Slug an...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Kejun, Chen, Dong, Jiao, Xuelong, Zhang, Shaoyan, Liu, Xiangping, Cao, Jingyu, Wu, Liqun, Wang, Dongsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125102/
https://www.ncbi.nlm.nih.gov/pubmed/21283078
http://dx.doi.org/10.1038/labinvest.2010.201
_version_ 1782207162671431680
author Zhang, Kejun
Chen, Dong
Jiao, Xuelong
Zhang, Shaoyan
Liu, Xiangping
Cao, Jingyu
Wu, Liqun
Wang, Dongsheng
author_facet Zhang, Kejun
Chen, Dong
Jiao, Xuelong
Zhang, Shaoyan
Liu, Xiangping
Cao, Jingyu
Wu, Liqun
Wang, Dongsheng
author_sort Zhang, Kejun
collection PubMed
description Slug, a member of the Snail family of transcription factors, has a crucial role in the regulation of epithelial-mesenchymal transition (EMT) by suppressing several epithelial markers and adhesion molecules, including E-cadherin. A recent study demonstrated that no relationship exists between Slug and E-cadherin in pancreatic cancer. Another study showed that in malignant mesothelioma effusions Slug was associated with matrix metalloproteinase (MMP) expression, but that there was no association with E-cadherin. F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. In this study, we investigated Slug, E-cadherin, and MMP-9 expression using immunohistochemistry in 60 patients with pancreatic cancer and their correlation with carcinoma invasion and metastasis. Additionally, we observed the effects of Slug on invasion and metastasis in the pancreatic cancer cell line PANC-1. Alterations in Slug, MMP-9, and E-cadherin were determined by RT-PCR, western blot, and immunohistochemistry. Alterations in MMP-9 and F-actin cytoskeleton were determined by immunofluorescence staining, flow cytometry (FCM), or gelatin zymography. Slug, E-cadherin, and MMP-9 expression in pancreatic cancer was significantly associated with lymph node metastases and we found a significant correlation between Slug and MMP-9 expression; however, no significant correlation was observed between Slug and E-cadherin expression. Slug transfection significantly increased invasion and metastasis in PANC-1 cells and orthotopic tumor of mouse in vivo, and significantly upregulated and activated MMP-9; however, there was no effect on E-cadherin expression. Slug promoted the formation of lamelliopodia or filopodia in PANC-1 cells. The intracellular F-actin and MMP-9 was increased and relocated to the front of the extending pseudopodia from the perinuclear pool in Slug-transfected PANC-1 cells. These results suggest that Slug promotes migration and invasion of PANC-1 cells, which may correlate with the reorganization of MMP-9 and remodeling of the F-actin cytoskeleton, but not with E-cadherin expression.
format Online
Article
Text
id pubmed-3125102
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-31251022011-06-29 Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling Zhang, Kejun Chen, Dong Jiao, Xuelong Zhang, Shaoyan Liu, Xiangping Cao, Jingyu Wu, Liqun Wang, Dongsheng Lab Invest Research Article Slug, a member of the Snail family of transcription factors, has a crucial role in the regulation of epithelial-mesenchymal transition (EMT) by suppressing several epithelial markers and adhesion molecules, including E-cadherin. A recent study demonstrated that no relationship exists between Slug and E-cadherin in pancreatic cancer. Another study showed that in malignant mesothelioma effusions Slug was associated with matrix metalloproteinase (MMP) expression, but that there was no association with E-cadherin. F-ascin is an actin-bundling protein involved in filopodia assembly and cancer invasion and metastasis of multiple epithelial cancer types. In this study, we investigated Slug, E-cadherin, and MMP-9 expression using immunohistochemistry in 60 patients with pancreatic cancer and their correlation with carcinoma invasion and metastasis. Additionally, we observed the effects of Slug on invasion and metastasis in the pancreatic cancer cell line PANC-1. Alterations in Slug, MMP-9, and E-cadherin were determined by RT-PCR, western blot, and immunohistochemistry. Alterations in MMP-9 and F-actin cytoskeleton were determined by immunofluorescence staining, flow cytometry (FCM), or gelatin zymography. Slug, E-cadherin, and MMP-9 expression in pancreatic cancer was significantly associated with lymph node metastases and we found a significant correlation between Slug and MMP-9 expression; however, no significant correlation was observed between Slug and E-cadherin expression. Slug transfection significantly increased invasion and metastasis in PANC-1 cells and orthotopic tumor of mouse in vivo, and significantly upregulated and activated MMP-9; however, there was no effect on E-cadherin expression. Slug promoted the formation of lamelliopodia or filopodia in PANC-1 cells. The intracellular F-actin and MMP-9 was increased and relocated to the front of the extending pseudopodia from the perinuclear pool in Slug-transfected PANC-1 cells. These results suggest that Slug promotes migration and invasion of PANC-1 cells, which may correlate with the reorganization of MMP-9 and remodeling of the F-actin cytoskeleton, but not with E-cadherin expression. Nature Publishing Group 2011-03 2011-01-31 /pmc/articles/PMC3125102/ /pubmed/21283078 http://dx.doi.org/10.1038/labinvest.2010.201 Text en Copyright © 2011 United States and Canadian Academy of Pathology, Inc.
spellingShingle Research Article
Zhang, Kejun
Chen, Dong
Jiao, Xuelong
Zhang, Shaoyan
Liu, Xiangping
Cao, Jingyu
Wu, Liqun
Wang, Dongsheng
Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title_full Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title_fullStr Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title_full_unstemmed Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title_short Slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
title_sort slug enhances invasion ability of pancreatic cancer cells through upregulation of matrix metalloproteinase-9 and actin cytoskeleton remodeling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125102/
https://www.ncbi.nlm.nih.gov/pubmed/21283078
http://dx.doi.org/10.1038/labinvest.2010.201
work_keys_str_mv AT zhangkejun slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT chendong slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT jiaoxuelong slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT zhangshaoyan slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT liuxiangping slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT caojingyu slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT wuliqun slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling
AT wangdongsheng slugenhancesinvasionabilityofpancreaticcancercellsthroughupregulationofmatrixmetalloproteinase9andactincytoskeletonremodeling