title: Annexin/S100A Protein Family Regulation through p14ARF-p53 Activation: A Role in Cell Survival and Predicting Treatment Outcomes in Breast Cancer.
abstract: 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.
authors.affiliation: School of Life Sciences, Faculty of Science, Faculty of Engineering and IT, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Diana
authors.initials: D
authors.lastname: Hatoum
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yagoub
authors.affiliation: Faculty of Engineering and IT, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ahadi
authors.affiliation: School of Life Sciences, Faculty of Science, Faculty of Engineering and IT, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Najah T
authors.initials: NT
authors.lastname: Nassif
authors.affiliation: School of Life Sciences, Faculty of Science, Faculty of Engineering and IT, University of Technology Sydney, Sydney, New South Wales, Australia.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: McGowan
mesh_terms: D017302:Annexins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D045744:Cell Line, Tumor; D002470:Cell Survival; D016000:Cluster Analysis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D053208:Kaplan-Meier Estimate; D005810:Multigene Family; D009928:Organ Specificity / Q000235:genetics; D011379:Prognosis; D011485:Protein Binding; D020543:Proteome; D040901:Proteomics / Q000379:methods; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016896:Treatment Outcome; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D017302:Annexins; D020543:Proteome; D009418:S100 Proteins; C110294:S100A1 protein; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53