BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer

Title: BAG3 promotes tumour cell proliferation by regulating EGFR signal transduction pathways in triple negative breast cancer
Authors: Shields, SarahConroy, EmerO'Grady, TonyMcGoldrick, AloysiusDempsey, EugeneReilly, RebeccaFan, YueMatallanas, DavidMcCann, AmandaGallagher, William M.Coppinger, Judith A.et al.
Permanent link: http://hdl.handle.net/10197/11891
Date: 20-Mar-2018
Online since: 2021-01-26T08:56:03Z
Abstract: Triple-negative breast cancer (TNBC), is a heterogeneous disease characterised by absence of expression of the estrogen receptor (ER), progesterone receptor (PR) and lack of amplification of human epidermal growth factor receptor 2 (HER2). TNBC patients can exhibit poor prognosis and high recurrence stages despite early response to chemotherapy treatment. In this study, we identified a pro-survival signalling protein BCL2- associated athanogene 3 (BAG3) to be highly expressed in a subset of TNBC cell lines and tumour tissues. High mRNA expression of BAG3 in TNBC patient cohorts significantly associated with a lower recurrence free survival. The epidermal growth factor receptor (EGFR) is amplified in TNBC and EGFR signalling dynamics impinge on cancer cell survival and disease recurrence. We found a correlation between BAG3 and EGFR expression in TNBC cell lines and determined that BAG3 can regulate tumour cell proliferation, migration and invasion in EGFR expressing TNBC cells lines. We identified an interaction between BAG3 and components of the EGFR signalling networks using mass spectrometry. Furthermore, BAG3 contributed to regulation of proliferation in TNBC cell lines by reducing the activation of components of the PI3K/AKT and FAK/Src signalling subnetworks. Finally, we found that combined targeting of BAG3 and EGFR was more effective than inhibition of EGFR with Cetuximab alone in TNBC cell lines. This study demonstrates a role for BAG3 in regulation of distinct EGFR modules and highlights the potential of BAG3 as a therapeutic target in TNBC.
Funding Details: Science Foundation Ireland
Funding Details: Irish Cancer Society Collaborative Cancer Research Centre
National Children’s Research Centre
Royal College of Surgeons in Ireland
Type of material: Journal Article
Publisher: Impact Journals
Journal: Oncotarget
Volume: 9
Issue: 21
Start page: 15673
End page: 15690
Copyright (published version): 2018 the Authors
Keywords: Breast cancerCancerTNBCBAG3EGFRSignallingProliferation
DOI: 10.18632/oncotarget.24590
Language: en
Status of Item: Peer reviewed
ISSN: 1949-2553
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by/3.0/ie/
Appears in Collections:Biology & Environmental Science Research Collection
SBI Research Collection
Biomolecular and Biomedical Science Research Collection
Medicine Research Collection

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