title: Native type IV collagen induces an epithelial to mesenchymal transition-like process in mammary epithelial cells MCF10A.
abstract: Basement membrane (BM) is a complex network of interacting proteins, including type IV collagen (Col IV) that acts as a scaffold that stabilizes the physical structures of tissues and regulates cellular processes. In the mammary gland, BM is a continuous deposit that separates epithelial cells from stroma, and its degradation is related with an increased potential for invasion and metastasis. Epithelial to mesenchymal transition (EMT) is a process by which epithelial cells are transdifferentiated to one mesenchymal state, and is a normal process during embryonic development, tissue remodeling and wound healing, as well as it has been implicated during cancer progression. In breast cancer cells, native Col IV induces migration and gelatinases secretion. However, the role of native Col IV on the EMT process in human mammary epithelial cells remains to be investigated. In the present study, we demonstrate that native Col IV induces down-regulation of E-cadherin expression, accompanied with an increase of Snail1, Snail2 and Sip1 transcripts. Native Col IV also induces an increase in N-cadherin and vimentin expression, an increase of MMP-2 secretion, the activation of FAK and NFκB, cell migration and invasion in MCF10A cells. In summary, these findings demonstrate, for the first time, that native Col IV induces an EMT-like process in MCF10A human mammary non-tumorigenic epithelial cells.
authors.affiliation: Departamento de Biología Celular, Cinvestav-IPN, Av IPN # 2508, San Pedro Zacatenco, Mexico, DF 07360, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Espinosa Neira
authors.forename: Eduardo Perez
authors.initials: EP
authors.lastname: Salazar
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D024141:Collagen Type IV / Q000502:physiology*; D000070819:Discoidin Domain Receptor 1; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000378:metabolism / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D024141:Collagen Type IV; C108381:GEMIN2 protein, human; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; C092030:DDR1 protein, human; D000070819:Discoidin Domain Receptor 1; D020794:Receptor Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2