Annexin/S100A protein family regulation through p14ARF-p53 activation: A role in cell survival and predicting treatment outcomes in breast cancer

Hatoum, D; Yagoub, D; Ahadi, A; Nassif, NT; McGowan, EM

Annexin/S100A protein family regulation through p14ARF-p53 activation: A role in cell survival and predicting treatment outcomes in breast cancer

Hatoum, D Yagoub, D Ahadi, A

Nassif, NT

McGowan, EM

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2017, 12 (1)
Issue Date:: 2017-01-01

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Field	Value	Language
dc.contributor.author	Hatoum, D	en_US
dc.contributor.author	Yagoub, D	en_US
dc.contributor.author	Ahadi, A https://orcid.org/0000-0002-2018-3065	en_US
dc.contributor.author	Nassif, NT https://orcid.org/0000-0003-2675-8322	en_US
dc.contributor.author	McGowan, EM https://orcid.org/0000-0001-6371-3751	en_US
dc.date.available	2016-12-22	en_US
dc.date.issued	2017-01-01	en_US
dc.identifier.citation	PLoS ONE, 2017, 12 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/77165
dc.description.abstract	© 2017 Hatoum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The annexin family and S100A associated proteins are important regulators of diverse calcium- dependent cellular processes including cell division, growth regulation and apoptosis. Dysfunction of individual annexin and S100A proteins is associated with cancer progression, metastasis and cancer drug resistance. This manuscript describes the novel finding of differential regulation of the annexin and S100A family of proteins by activation of p53 in breast cancer cells. Additionally, the observed differential regulation is found to be beneficial to the survival of breast cancer cells and to influence treatment efficacy. We have used unbiased, quantitative proteomics to determine the proteomic changes occurring post p14ARF-p53 activation in estrogen receptor (ER) breast cancer cells. In this report we identified differential regulation of the annexin/S100A family, through unique peptide recognition at the N-terminal regions, demonstrating p14ARF-p53 is a central orchestrator of the annexin/S100A family of calcium regulators in favor of pro-survival functions in the breast cancer cell. This regulation was found to be cell-type specific. Retrospective human breast cancer studies have demonstrated that tumors with functional wild type p53 (p53wt) respond poorly to some chemotherapy agents compared to tumors with a non-functional p53. Given that modulation of calcium signaling has been demonstrated to change sensitivity of chemotherapeutic agents to apoptotic signals, in principle, we explored the paradigm of how p53 modulation of calcium regulators in ER+ breast cancer patients impacts and influences therapeutic outcomes.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0169925	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Breast Neoplasms	en_US
dc.subject.mesh	Annexins	en_US
dc.subject.mesh	S100 Proteins	en_US
dc.subject.mesh	Proteome	en_US
dc.subject.mesh	Prognosis	en_US
dc.subject.mesh	Treatment Outcome	en_US
dc.subject.mesh	Cluster Analysis	en_US
dc.subject.mesh	Proteomics	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Organ Specificity	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.subject.mesh	Protein Binding	en_US
dc.subject.mesh	Multigene Family	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Tumor Suppressor Protein p53	en_US
dc.subject.mesh	Tumor Suppressor Protein p14ARF	en_US
dc.subject.mesh	Kaplan-Meier Estimate	en_US
dc.title	Annexin/S100A protein family regulation through p14ARF-p53 activation: A role in cell survival and predicting treatment outcomes in breast cancer	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	12	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Computer Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	12	en_US

Abstract:

© 2017 Hatoum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The annexin family and S100A associated proteins are important regulators of diverse calcium- dependent cellular processes including cell division, growth regulation and apoptosis. Dysfunction of individual annexin and S100A proteins is associated with cancer progression, metastasis and cancer drug resistance. This manuscript describes the novel finding of differential regulation of the annexin and S100A family of proteins by activation of p53 in breast cancer cells. Additionally, the observed differential regulation is found to be beneficial to the survival of breast cancer cells and to influence treatment efficacy. We have used unbiased, quantitative proteomics to determine the proteomic changes occurring post p14ARF-p53 activation in estrogen receptor (ER) breast cancer cells. In this report we identified differential regulation of the annexin/S100A family, through unique peptide recognition at the N-terminal regions, demonstrating p14ARF-p53 is a central orchestrator of the annexin/S100A family of calcium regulators in favor of pro-survival functions in the breast cancer cell. This regulation was found to be cell-type specific. Retrospective human breast cancer studies have demonstrated that tumors with functional wild type p53 (p53wt) respond poorly to some chemotherapy agents compared to tumors with a non-functional p53. Given that modulation of calcium signaling has been demonstrated to change sensitivity of chemotherapeutic agents to apoptotic signals, in principle, we explored the paradigm of how p53 modulation of calcium regulators in ER+ breast cancer patients impacts and influences therapeutic outcomes.

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http://hdl.handle.net/10453/77165