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RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones
BACKGROUND: Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mi...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846889/ https://www.ncbi.nlm.nih.gov/pubmed/20236512 http://dx.doi.org/10.1186/1476-4598-9-61 |
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author | Peruta, Marco Della Giagulli, Cinzia Laudanna, Carlo Scarpa, Aldo Sorio, Claudio |
author_facet | Peruta, Marco Della Giagulli, Cinzia Laudanna, Carlo Scarpa, Aldo Sorio, Claudio |
author_sort | Peruta, Marco Della |
collection | PubMed |
description | BACKGROUND: Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides. METHODS: Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting RESULTS: When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 μm pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides. CONCLUSION: Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC. |
format | Text |
id | pubmed-2846889 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28468892010-03-30 RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones Peruta, Marco Della Giagulli, Cinzia Laudanna, Carlo Scarpa, Aldo Sorio, Claudio Mol Cancer Research BACKGROUND: Our understanding of the mechanism regulating pancreatic cancer metastatic phenotype is limited. We analyzed the role of RHOA and PRKCZ in the motility attitude of two subclones of the pancreatic adenocarcinoma cell line SUIT-2 (S2), with different in vivo metastatic potential in nude mice: S2-m with a low metastatic potential and highly metastatic S2-CP9 using RHOA and PRKCZ cell-permeable inhibitory peptides. METHODS: Adhesion assays, cell permeable peptides, RHOA activity assay, western blotting RESULTS: When used in combination cell-permeable inhibitory peptides partially inhibited cell adhesion by about 50% in clone S2-CP9. In clone S2-m, the effect was limited to 15% inhibition. In a wound healing assay, S2-CP9 was sensitive only to treatment with the combination of both RHOA and PRKCZ inhibitory peptides. Conversely, S2-m was unable to migrate toward both ends of the wound in basal conditions. Migration of cells through a membrane with 8 μm pores was completely abolished in both clones by individual treatment with RHOA and PRKCZ inhibitory peptides. CONCLUSION: Herein, we demonstrate a critical role for RHOA and PRKCZ in the regulation of different aspects of cell motility of pancreatic adenocarcinoma and demonstrate the need to inhibit both pathways to obtain a functionally relevant effect in most assays. These results indicate that RHOA and PRKCZ, and their downstream effectors, can represent important pharmacological targets that could potentially control the highly metastatic attitude of PDAC. BioMed Central 2010-03-17 /pmc/articles/PMC2846889/ /pubmed/20236512 http://dx.doi.org/10.1186/1476-4598-9-61 Text en Copyright ©2010 Peruta et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Peruta, Marco Della Giagulli, Cinzia Laudanna, Carlo Scarpa, Aldo Sorio, Claudio RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title | RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title_full | RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title_fullStr | RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title_full_unstemmed | RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title_short | RHOA and PRKCZ control different aspects of cell motility in pancreatic cancer metastatic clones |
title_sort | rhoa and prkcz control different aspects of cell motility in pancreatic cancer metastatic clones |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846889/ https://www.ncbi.nlm.nih.gov/pubmed/20236512 http://dx.doi.org/10.1186/1476-4598-9-61 |
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