title: Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid.
abstract: In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression.
authors: Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors: Valentina
authors: V
authors: Bizzarro
authors: Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors: Raffaella
authors: R
authors: Belvedere
authors: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors: Maria Rita
authors: MR
authors: Milone
authors: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors: Biagio
authors: B
authors: Pucci
authors: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors: Rita
authors: R
authors: Lombardi
authors: Experimental Pharmacology Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors: Francesca
authors: F
authors: Bruzzese
authors: Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors: Ada
authors: A
authors: Popolo
authors: Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors: Luca
authors: L
authors: Parente
authors: Centro Ricerche Oncologiche Mercogliano, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.|Experimental Pharmacology Unit, Istituto Nazionale Tumori Fondazione G. Pascale - IRCCS, Naples, Italy.
authors: Alfredo
authors: A
authors: Budillon
authors: Department of Pharmacy, University of Salerno, Fisciano (SA), Italy.
authors: Antonello
authors: A
authors: Petrella
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D000077211:Zoledronic Acid
chemical_list: D018528:ATP-Binding Cassette Transporters; D017305:Annexin A1; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: EMT; annexin A1; cancer stem cells; cell invasion; prostate cancer