title: A Novel Role of E-Cadherin-Based Adherens Junctions in Neoplastic Cell Dissemination.
abstract: Using confocal microscopy, we analyzed the behavior of IAR-6-1, IAR1170, and IAR1162 transformed epithelial cells seeded onto the confluent monolayer of normal IAR-2 epithelial cells. Live-cell imaging of neoplastic cells stably expressing EGFP and of normal epithelial cells stably expressing mKate2 showed that transformed cells retaining expression of E-cadherin were able to migrate over the IAR-2 epithelial monolayer and invade the monolayer. Transformed IAR cells invaded the IAR-2 monolayer at the boundaries between normal cells. Studying interactions of IAR-6-1 transformed cells stably expressing GFP-E-cadherin with the IAR-2 epithelial monolayer, we found that IAR-6-1 cells established E-cadherin-based adhesions with normal epithelial cells: dot-like dynamic E-cadherin-based adhesions in protrusions and large adherens junctions at the cell sides and rear. A comparative study of a panel of transformed IAR cells that differ by their ability to form E-cadherin-based AJs, either through loss of E-cadherin expression or through expression of a dominant negative E-cadherin mutant, demonstrated that E-cadherin-based AJs are key mediators of the interactions between neoplastic and normal epithelial cells. IAR-6-1DNE cells expressing a dominant-negative mutant form of E-cadherin with the mutation in the first extracellular domain practically lost the ability to adhere to IAR-2 cells and invade the IAR-2 epithelial monolayer. The ability of cancer cells to form E-cadherin-based AJs with the surrounding normal epithelial cells may play an important role in driving cancer cell dissemination in the body.
authors.affiliation: Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Rubtsova
authors.affiliation: Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors.forename: Irina Y
authors.initials: IY
authors.lastname: Zhitnyak
authors.affiliation: Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.
authors.forename: Natalya A
authors.initials: NA
authors.lastname: Gloushankova
mesh_terms: D022005:Adherens Junctions; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002461:Cell Line, Transformed; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000528:radiation effects; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014161:Transduction, Genetic; D057705:Transendothelial and Transepithelial Migration / Q000502:physiology*; D014162:Transfection
chemical_list: D015820:Cadherins; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins