title: Proteomics analysis of E-cadherin knockdown in epithelial breast cancer cells.
abstract: E-cadherin is the core protein of the epithelial adherens junction. Through its cytoplasmic domain, E-cadherin interacts with several signaling proteins; among them, α- and β-catenins mediate the link of E-cadherin to the actin cytoskeleton. Loss of E-cadherin expression is a crucial step of epithelial-mesenchymal transition (EMT) and is involved in cancer invasion and metastatization. In human tumors, down-regulation of E-cadherin is frequently associated with poor prognosis. Despite the critical role of E-cadherin in cancer progression, little is known about proteome alterations linked with its down-regulation. To address this point, we investigated proteomics, biophysical and functional changes of epithelial breast cancer cell lines upon shRNA-mediated stable knockdown of E-cadherin expression (shEcad). shEcad cells showed a distinct proteomic signature including altered expression of enzymes and proteins involved in cytoskeletal dynamic and migration. Moreover, these results suggest that, besides their role in mechanical adhesion, loss of E-cadherin expression may contribute to cancer progression by modifying a complex network of pathways that tightly regulate fundamental processes as oxidative stress, immune evasion and cell metabolism. Altogether, these results extend our knowledge on the cellular modifications associated with E-cadherin down-regulation in breast cancer cells.
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy; Laboratory of Clinical Proteomic, "Giovanni Paolo II" Hospital, ASL-Lecce, Italy. Electronic address: danielevergara@libero.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vergara
authors.affiliation: Unit of Cancer Pathology, and Department of Neuroscience and Imaging, Research Centre on Aging (Ce.S.I), "G. d'Annunzio" University Foundation, Chieti-Pescara, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Simeone
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy; Laboratory of Clinical Proteomic, "Giovanni Paolo II" Hospital, ASL-Lecce, Italy.
authors.forename: Dominga
authors.initials: D
authors.lastname: Latorre
authors.affiliation: NNL-Istituto Nanoscienze, CNR, Via Arnesano, Lecce, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cascione
authors.affiliation: NNL-Istituto Nanoscienze, CNR, Via Arnesano, Lecce, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Leporatti
authors.affiliation: Unit of Cancer Pathology, and Department of Neuroscience and Imaging, Research Centre on Aging (Ce.S.I), "G. d'Annunzio" University Foundation, Chieti-Pescara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Trerotola
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Giudetti
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Capobianco
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lunetti
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Rizzello
authors.affiliation: NNL-Istituto Nanoscienze, CNR, Via Arnesano, Lecce, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Rinaldi
authors.affiliation: Unit of Cancer Pathology, and Department of Neuroscience and Imaging, Research Centre on Aging (Ce.S.I), "G. d'Annunzio" University Foundation, Chieti-Pescara, Italy.
authors.forename: Saverio
authors.initials: S
authors.lastname: Alberti
authors.affiliation: Department of Biological and Environmental Sciences and Technologies, University of Salento, Via Monteroni, Lecce, Italy; Laboratory of Clinical Proteomic, "Giovanni Paolo II" Hospital, ASL-Lecce, Italy. Electronic address: michele.maffia@unisalento.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Maffia
mesh_terms: D015703:Antigens, CD; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000037:antagonists & inhibitors* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D040901:Proteomics / Q000379:methods*; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering
keywords: E-cadherin; Epithelial mesenchymal-transition; Proteomics