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.
Highlights
Classical cadherins are transmembrane glycoproteins that mediate cell-cell adhesion through Ca+2-dependent homophilic trans-interactions of their ectodomains, forming adherens junctions (AJs) [1]
The E-cadherin-based AJs in IAR-2 cells aligned as continuous belts along the cell-cell boundaries, and co-localized with the circumferential actin bundles (Fig 1C)
Arp2/3-mediated polymerization of actin network at the leading edge followed by formation of focal adhesions and pericellular proteolysis of extracellular matrix are key to mesenchymal movement
Summary
Classical cadherins are transmembrane glycoproteins that mediate cell-cell adhesion through Ca+2-dependent homophilic trans-interactions of their ectodomains, forming adherens junctions (AJs) [1]. In AJs, intracellular domains of cadherins interact with catenins, which in turn interact with actin and several actin-binding proteins. Actin filaments are essential for the stability of AJs. E-cadherin plays a key role in the maintenance of stable cell-cell adhesion in epithelial tissues. Epithelial-mesenchymal transition (EMT) has been regarded as the trigger for invasion and metastasis of carcinoma cells [2].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
