title: Effect of microtubule-targeting drugs on cell-cell and cell-matrix junctions in tumor epithelial cells.
abstract: In this study, we investigated the effects of microtubule-targeting drugs, which either destabilize (the Vinca alkaloid vincristine) or stabilize (the taxane derivative docetaxel) microtubules, on the cell-cell and cell-matrix adhesive junctions of Caco-2 tumor epithelial cells, using fluorescence imaging and functional assays. We found that, in sub-confluent (but not confluent) cells, vincristine (but not docetaxel) affected cell-cell junction morphology. Furthermore, docetaxel (but not vincristine) attenuated the formation of the peri-junctional actomyosin ring and enhanced the internalization of junctional adhesion molecule-A. However, these effects of vincristine and docetaxel did not translate into appreciable functional changes during the opening and resealing of the cell-cell junctions. We also found that vincristine caused enlargement of focal adhesions (the major cell-matrix junctions) without affecting cell adhesion onto the matrix. Thus, we conclude that the microtubule-targeting drugs interfere to variable degrees with the morphology and/or function of the cell-cell and cell-matrix adhesive junctions. In addition, the results highlight the importance of considering the cellular context and dynamics (e.g. cell confluence and junction opening, respectively), when determining the final effects of microtubule manipulation on cell adhesiveness.
authors.affiliation: Mario Negri Institute of Pharmacological Research, Milano, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tonutti
authors.forename: Elena
authors.initials: E
authors.lastname: Bononi
authors.forename: Luca
authors.initials: L
authors.lastname: Paris
authors.forename: Fabienne
authors.initials: F
authors.lastname: Breillout
authors.forename: Nathalie
authors.initials: N
authors.lastname: Corvaia
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Bazzoni
mesh_terms: D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D021982:Cell-Matrix Junctions / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects*; D062726:Junctional Adhesion Molecules; D008870:Microtubules / Q000187:drug effects* / Q000473:pathology; D058990:Molecular Targeted Therapy; D043823:Taxoids / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D062726:Junctional Adhesion Molecules; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; D014750:Vincristine