title: Tracking the intermediate stages of epithelial-mesenchymal transition in epithelial stem cells and cancer.
abstract: Epithelial-mesenchymal transition (EMT) is an essential developmental program that becomes reactivated in adult tissues to promote the progression of cancer. EMT has been largely studied by examining the beginning epithelial state or the ending mesenchymal state without studying the intermediate stages. Recent studies using trophoblast stem (TS) cells paused in EMT have defined the molecular and epigenetic mechanisms responsible for modulating the intermediate "metastable" stages of EMT. Targeted inactivation of MAP3K4, knockdown of CBP, or overexpression of SNAI1 in TS cells induced similar metastable phenotypes. These TS cells exhibited epigenetic changes in the histone acetylation landscape that cause loss of epithelial maintenance while preserving self-renewal and multipotency. A similar phenotype was found in claudin-low breast cancer cells with properties of EMT and stemness. This intersection between EMT and stemness in TS cells and claudin-low metastatic breast cancer demonstrates the usefulness of developmental EMT systems to understand EMT in cancer.
authors.affiliation: Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, USA. nicole_vincent@med.unc.edu
authors.forename: Nicole Vincent
authors.initials: NV
authors.lastname: Jordan
authors.forename: Gary L
authors.initials: GL
authors.lastname: Johnson
authors.forename: Amy N
authors.initials: AN
authors.lastname: Abell
mesh_terms: D000107:Acetylation; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D051519:Fibroblast Growth Factor 4 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D048768:MAP Kinase Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D010920:Placenta / Q000473:pathology; D011247:Pregnancy; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015820:Cadherins; C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D048768:MAP Kinase Kinase Kinase 4; C482780:Map3k4 protein, mouse