Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620496
Title:
Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways.
Authors:
Pranjol, M. Z. I.; Gutowski, Nicholas J.; Hannemann, Michael; Whatmore, J. L.
Abstract:
Epithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i.e. proliferation and migration, to investigate whether these effects are dependent on CathD catalytic activity and to delineate the intracellular signalling kinases activated by CathD. We report, for the first time, that CathD significantly increases HOMEC proliferation and migration via a non-proteolytic mechanism resulting in activation of ERK1/2 and AKT. These data suggest that EOC cancer secreted CathD acts as an extracellular ligand and may play an important pro-angiogenic, and thus pro-metastatic, role by activating the omental microvasculature during EOC metastasis to the omentum.
Citation:
Cathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways. 2017, 1865 (1):25-33 Biochim. Biophys. Acta
Publisher:
Elsevier
Journal:
Biochimica et biophysica acta
Issue Date:
10-Oct-2017
URI:
http://hdl.handle.net/11287/620496
DOI:
10.1016/j.bbamcr.2017.10.005
PubMed ID:
29024694
Additional Links:
https://linkinghub.elsevier.com/retrieve/pii/S0167-4889(17)30272-0
Type:
Journal Article
Language:
en
ISSN:
0006-3002
Appears in Collections:
Neurology; Obstetrics, Gynaecology & Maternity Services; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPranjol, M. Z. I.en
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorHannemann, Michaelen
dc.contributor.authorWhatmore, J. L.en
dc.date.accessioned2017-11-10T14:14:31Z-
dc.date.available2017-11-10T14:14:31Z-
dc.date.issued2017-10-10-
dc.identifier.citationCathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways. 2017, 1865 (1):25-33 Biochim. Biophys. Actaen
dc.identifier.issn0006-3002-
dc.identifier.pmid29024694-
dc.identifier.doi10.1016/j.bbamcr.2017.10.005-
dc.identifier.urihttp://hdl.handle.net/11287/620496-
dc.description.abstractEpithelial ovarian cancer (EOC) frequently metastasises to the omentum, a process that requires pro-angiogenic activation of human omental microvascular endothelial cells (HOMECs) by tumour-secreted factors. We have previously shown that ovarian cancer cells secrete a range of factors that induce pro-angiogenic responses e.g. migration, in HOMECs including the lysosomal protease cathepsin D (CathD). However, the cellular mechanism by which CathD induces these cellular responses is not understood. The aim of this study was to further examine the pro-angiogenic effects of CathD in HOMECs i.e. proliferation and migration, to investigate whether these effects are dependent on CathD catalytic activity and to delineate the intracellular signalling kinases activated by CathD. We report, for the first time, that CathD significantly increases HOMEC proliferation and migration via a non-proteolytic mechanism resulting in activation of ERK1/2 and AKT. These data suggest that EOC cancer secreted CathD acts as an extracellular ligand and may play an important pro-angiogenic, and thus pro-metastatic, role by activating the omental microvasculature during EOC metastasis to the omentum.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S0167-4889(17)30272-0en
dc.rightsArchived with thanks to Biochimica et biophysica actaen
dc.subjectWessex Classification Subject Headings::Gynaecologyen
dc.titleCathepsin D non-proteolytically induces proliferation and migration in human omental microvascular endothelial cells via activation of the ERK1/2 and PI3K/AKT pathways.en
dc.typeJournal Articleen
dc.identifier.journalBiochimica et biophysica actaen
dc.type.versionPublisheden

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