title: E-Cadherin repression increases amount of cancer stem cells in human A549 lung adenocarcinoma and stimulates tumor growth.
abstract: Here we show that cancer stem cells amount in human lung adenocarcinoma cell line A549 depends on E-cadherin expression. In fact, downregulation of E-cadherin expression enhanced expression of pluripotent genes (c-MYC, NESTIN, OCT3/4 and SOX2) and enriched cell population with the cells possessing the properties of so-called 'cancer stem cells' via activation of Wnt/β-catenin signaling. Repression of E-cadherin also stimulated cell proliferation and migration in vitro, decreased cell amount essential for xenografts formation in nude mice, increased tumors vascularization and growth. On the other hand, E-cadherin upregulation caused opposite effects i.e. diminished the number of cancer stem cells, decreased xenograft vascularization and decelerated tumor growth. Therefore, agents restoring E-cadherin expression may be useful in anticancer therapy.
authors.affiliation: a Blokhin Russian Cancer Research Center , Moscow , Russia.
authors.forename: M
authors.initials: M
authors.lastname: Farmakovskaya
authors.affiliation: a Blokhin Russian Cancer Research Center , Moscow , Russia.
authors.forename: N
authors.initials: N
authors.lastname: Khromova
authors.affiliation: a Blokhin Russian Cancer Research Center , Moscow , Russia.
authors.forename: V
authors.initials: V
authors.lastname: Rybko
authors.affiliation: b Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University , Moscow , Russia.
authors.forename: V
authors.initials: V
authors.lastname: Dugina
authors.affiliation: a Blokhin Russian Cancer Research Center , Moscow , Russia.
authors.forename: B
authors.initials: B
authors.lastname: Kopnin
authors.affiliation: a Blokhin Russian Cancer Research Center , Moscow , Russia.
authors.forename: P
authors.initials: P
authors.lastname: Kopnin
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D002452:Cell Count; D049109:Cell Proliferation; D048430:Cell Shape; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008819:Mice, Nude; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; D012097:Repressor Proteins
keywords: B-catenin; E-cadherin; cancer stem cells (CSCs); tumor progression; wnt-signaling