title: High-throughput molecular profiling of a P-cadherin overexpressing breast cancer model reveals new targets for the anti-cancer bacterial protein azurin.
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.
authors: Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: Nuno
authors: N
authors: Bernardes
authors: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: Ana Sofia
authors: AS
authors: Ribeiro
authors: Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal.
authors: Sofia
authors: S
authors: Abreu
authors: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: André F
authors: AF
authors: Vieira
authors: Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal.
authors: Laura
authors: L
authors: Carreto
authors: Department of Biology and CESAM, University of Aveiro, Aveiro, Portugal.
authors: Manuel
authors: M
authors: Santos
authors: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: Raquel
authors: R
authors: Seruca
authors: Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors: Joana
authors: J
authors: Paredes
authors: Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Técnico, Lisbon, Portugal. Electronic address: afialho@ist.utl.pt.
authors: Arsenio M
authors: AM
authors: Fialho
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001400:Azurin / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D016023:Integrins / Q000096:biosynthesis / Q000235:genetics; D061986:MCF-7 Cells; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D016023:Integrins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D001400:Azurin
keywords: Azurin; Breast cancer; Integrin; P-cadherin; cDNA microarrays