Type

Journal Article

Authors

Martin Clynes
Ray McDermott
Paul Dowling
Kevin Conlon
Niall Swan
Anne-Marie Larkin
Naomi Walsh

Subjects

Biochemistry

Topics
prevention control antagonists inhibitors cell biology cancer therapy signal transduction invasion cell movement genetics rna small interfering pathology metabolism pancreatic neoplasms cancer cells mmp2 cancer cell lines adenocarcinoma mucinous hsp90 matrix metalloproteinases immunoenzyme techniques cancer matrix metalloproteinase 2 gene expression regulation neoplastic molecular chaperones hsp70 heat shock proteins blotting western immunoprecipitation hsp90 heat shock proteins tumor cells cultured secondary cell adhesion hop neoplasm invasiveness organising protein stip1 stress induced phosphoprotein 1 heat shock proteins pancreatic cancer humans stip1 protein human cancer patients down regulation matrix metalloproteinase inhibitors carcinoma pancreatic ductal

RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation (2011)

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.
Collections Ireland -> Dublin City University -> Publication Type = Article
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering: Biology
Ireland -> Dublin City University -> Subject = Biological Sciences: Cell biology
Ireland -> Dublin City University -> Status = Published
Ireland -> Maynooth University -> Status = Published
Ireland -> Maynooth University -> Open Access DRIVERset
Ireland -> Dublin City University -> DCU Faculties and Centres = Research Initiatives and Centres: National Institute for Cellular Biotechnology (NICB)
Ireland -> Dublin City University -> DCU Faculties and Centres = Research Initiatives and Centres
Ireland -> Dublin City University -> Subject = Medical Sciences: Cancer
Ireland -> Dublin City University -> Subject = Biological Sciences
Ireland -> Maynooth University -> Type = Article
Ireland -> Dublin City University -> Subject = Medical Sciences
Ireland -> Maynooth University -> Academic Unit = Faculty of Science and Engineering

Full list of authors on original publication

Martin Clynes, Ray McDermott, Paul Dowling, Kevin Conlon, Niall Swan, Anne-Marie Larkin, Naomi Walsh

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
Paul Dowling
Dublin City University
Total Publications: 79
 
3
N Swan
IT Tallaght
Total Publications: 19
 
4
Anne-Marie Larkin
Dublin City University
Total Publications: 6
 
5
Naomi Walsh
Dublin City University
Total Publications: 18