Hanna A. Zielinska
Interaction between GRP78 and IGFBP-3 affects tumourigenesis and prognosis in breast cancer patients
Zielinska, Hanna A.; Daly, Carl S.; Alghamdi, Ahmad; Bahl, Amit; Sohail, Muhammed; White, Paul; Holly, Jeff M. P.; Dean, Sarah R.; Perks, Claire M.
Authors
Carl S. Daly
Ahmad Alghamdi
Amit Bahl
Muhammed Sohail
Paul White Paul.White@uwe.ac.uk
Professor in Applied Statistics
Jeff M. P. Holly
Sarah Dean Sarah4.Dean@uwe.ac.uk
Senior Lecturer in Biomedical Science
Claire M. Perks
Abstract
Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients.
Journal Article Type | Article |
---|---|
Acceptance Date | Dec 15, 2020 |
Online Publication Date | Dec 18, 2020 |
Publication Date | Dec 18, 2020 |
Deposit Date | Feb 14, 2021 |
Publicly Available Date | Feb 18, 2021 |
Journal | Cancers |
Electronic ISSN | 2072-6694 |
Publisher | MDPI |
Peer Reviewed | Peer Reviewed |
Volume | 12 |
Issue | 12 |
Article Number | 3821 |
Pages | 1-13 |
DOI | https://doi.org/10.3390/cancers12123821 |
Keywords | Cancer Research; Oncology; breast cancer prognosis; GRP78; IGFBP-3; metastasis |
Public URL | https://uwe-repository.worktribe.com/output/6972736 |
Files
Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients
(1.9 Mb)
PDF
Licence
http://creativecommons.org/licenses/by/4.0/
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
You might also like
Test statistics for comparing two proportions with partially overlapping samples
(2015)
Journal Article
Women's views and experiences of antenatal enquiry for domestic abuse during pregnancy
(2015)
Journal Article
Downloadable Citations
About UWE Bristol Research Repository
Administrator e-mail: repository@uwe.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search