RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.

Hdl Handle:
http://hdl.handle.net/10147/251936
Title:
RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.
Authors:
Walsh, Naomi; Larkin, AnneMarie; Swan, Niall; Conlon, Kevin; Dowling, Paul; McDermott, Ray; Clynes, Martin
Affiliation:
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. Naomi.walsh@dcu.ie
Citation:
RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. 2011, 306 (2):180-9 Cancer Lett.
Publisher:
Cancer letters
Journal:
Cancer letters
Issue Date:
28-Jul-2011
URI:
http://hdl.handle.net/10147/251936
DOI:
10.1016/j.canlet.2011.03.004
PubMed ID:
21470770
Abstract:
We previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.
Item Type:
Article
Language:
en
MeSH:
Adenocarcinoma, Mucinous; Blotting, Western; Carcinoma, Pancreatic Ductal; Cell Adhesion; Cell Movement; Down-Regulation; Gene Expression Regulation, Neoplastic; HSP70 Heat-Shock Proteins; HSP90 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Immunoenzyme Techniques; Immunoprecipitation; Matrix Metalloproteinase 2; Molecular Chaperones; Neoplasm Invasiveness; Pancreatic Neoplasms; RNA, Small Interfering; Tumor Cells, Cultured
ISSN:
1872-7980

Full metadata record

DC FieldValue Language
dc.contributor.authorWalsh, Naomien_GB
dc.contributor.authorLarkin, AnneMarieen_GB
dc.contributor.authorSwan, Niallen_GB
dc.contributor.authorConlon, Kevinen_GB
dc.contributor.authorDowling, Paulen_GB
dc.contributor.authorMcDermott, Rayen_GB
dc.contributor.authorClynes, Martinen_GB
dc.date.accessioned2012-11-13T09:28:16Z-
dc.date.available2012-11-13T09:28:16Z-
dc.date.issued2011-07-28-
dc.identifier.citationRNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. 2011, 306 (2):180-9 Cancer Lett.en_GB
dc.identifier.issn1872-7980-
dc.identifier.pmid21470770-
dc.identifier.doi10.1016/j.canlet.2011.03.004-
dc.identifier.urihttp://hdl.handle.net/10147/251936-
dc.description.abstractWe previously identified Hop as over expressed in invasive pancreatic cancer cell lines and malignant tissues of pancreatic cancer patients, suggesting an important role for Hop in the biology of invasive pancreatic cancer. Hop is a co-chaperone protein that binds to both Hsp70/Hsp90. We hypothesised that by targeting Hop, signalling pathways modulating invasion and client protein stabilisation involving Hsp90-dependent complexes may be altered. In this study, we show that Hop knockdown by small interfering (si)RNA reduces the invasion of pancreatic cancer cells, resulting in decreased expression of the downstream target gene, matrix metalloproteinases-2 (MMP-2). Hop in conditioned media co-immunoprecipitates with MMP-2, implicating a possible extracellular function for Hop. Knockdown of Hop expression also reduced expression levels of Hsp90 client proteins, HER2, Bcr-Abl, c-MET and v-Src. Furthermore, Hop is strongly expressed in high grade PanINs compared to lower PanIN grades, displaying differential localisation in invasive ductal pancreatic cancer, indicating that the localisation of Hop is an important factor in pancreatic tumours. Our data suggests that the attenuation of Hop expression inactivates key signal transduction proteins which may decrease the invasiveness of pancreatic cancer cells possibly through the modulation of Hsp90 activity. Therefore, targeting Hop in pancreatic cancer may constitute a viable strategy for targeted cancer therapy.en_GB
dc.language.isoenen
dc.publisherCancer lettersen_GB
dc.rightsArchived with thanks to Cancer lettersen_GB
dc.subject.meshAdenocarcinoma, Mucinous-
dc.subject.meshBlotting, Western-
dc.subject.meshCarcinoma, Pancreatic Ductal-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Movement-
dc.subject.meshDown-Regulation-
dc.subject.meshGene Expression Regulation, Neoplastic-
dc.subject.meshHSP70 Heat-Shock Proteins-
dc.subject.meshHSP90 Heat-Shock Proteins-
dc.subject.meshHeat-Shock Proteins-
dc.subject.meshHumans-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshImmunoprecipitation-
dc.subject.meshMatrix Metalloproteinase 2-
dc.subject.meshMolecular Chaperones-
dc.subject.meshNeoplasm Invasiveness-
dc.subject.meshPancreatic Neoplasms-
dc.subject.meshRNA, Small Interfering-
dc.subject.meshTumor Cells, Cultured-
dc.titleRNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation.en_GB
dc.typeArticleen
dc.contributor.departmentNational Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. Naomi.walsh@dcu.ieen_GB
dc.identifier.journalCancer lettersen_GB
dc.description.provinceLeinsteren

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.