High-throughput molecular profiling of a P-cadherin overexpressing breast cancer model reveals new targets for the anti-cancer bacterial protein azurin |
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| Affiliation: | 1. Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal;2. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal;3. Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal;1. Structural Chemistry Program, Eskitis Institute, Griffith University, Brisbane, Queensland, Australia;2. Centre for Biodiscovery and Molecular Development of Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Queensland, Australia;3. Université Lyon 1, Villeurbanne cedex, and Laboratoire Chimie et Biologie des Membranes et des Nanoobjets, Université Bordeaux, CBMN, UMR 5248, 33600 Pessac, France;4. Institute for Structural Biology, School of Biological Sciences, The University of Edinburgh, Scotland, UK;5. School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia;6. Queensland Institute of Medical Research, Herston, Queensland, Australia;7. Biology Division, California Institute of Technology, Pasadena, CA, USA;8. Faculty of Veterinary Science, The University of Melbourne, Parkville, Victoria, Australia;1. Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N. St. Clair, Suite 800, Chicago, IL 60611;2. Department of Medicine, Division of Hematology and Oncology, Northwestern University, 676 N. St. Clair, Suite 800, Chicago, IL 60611;3. Department of Surgery, Division of Transplantation, Comprehensive Transplant Center, Northwestern University, 676 N. St. Clair, Suite 800, Chicago, IL 60611;4. Department of Medicine, Division of Hematology, Northwestern University, 676 N. St. Clair, Suite 800, Chicago, IL 60611;1. Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece;2. Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;3. Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;4. Health Data Specialists Ltd., Athens, Greece;5. Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;6. First Department of Otorhinolaryngology, “AHEPA” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;7. ENT Department, “G. Papanikolaou” General Hospital, Thessaloniki, Greece;8. Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece |
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| Abstract: | Azurin is a bacterial protein from Pseudomonas aeruginosa which exerts an inhibitory activity in cancer cells. In P-cadherin-overexpressing models, a bad prognosis marker in breast cancer increasing invasion and other malignant features, azurin decreases the invasion of cancer cells.We performed a microarray analysis to compare the expression profile of azurin treated cells with different P-cadherin expression levels. Azurin up-regulated apoptosis mediated by p53 protein, endocytosis and vesicle-mediated transport. In the contrary, in invasive MCF-7/AZ.Pcad cells, azurin decreased the expression of genes associated with cell surface receptors and signal transduction, as well as biological adhesion. Further, azurin decreased adhesion of cells to proteins from the extracellular matrix (ECM) and altered protein expression of integrins α6, β4 and β1 and interfered with the ability of these cells to form mammospheres. Altogether, our results further enlighten the anti-cancer effects mediated by azurin in P-cadherin overexpression breast cancer models. |
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| Keywords: | Azurin P-cadherin cDNA microarrays Breast cancer Integrin |
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