ACQUISITION OF CELL-ADHESION AND INDUCTION OF FOCAL ADHESION KINASE OF HUMAN COLON-CANCER COLO-201 CELLS BY RETINOIC ACID-INDUCED DIFFERENTIATION

The human colon adenocarcinoma cell lines Colo 201 and Cole 205 lose a dhevise capacity to the extracellular matrix (ECM) and take on a round and floating cell shape. Treatment of these cells with all-trans-reti noic acid (RA) results in inhibition of growth and in a marked increas e in the production of carcinoembryonic antigen, thereby indicating th at the cells undergo differentiation. This RA-induced differentiation was accompanied by a large increase in the degree of cell adhesion wit h localization of E-cadherin molecules at cell-cell contact sites. We examined several adhesion molecules involved in cell-cell and cell-ECM interaction by immunoblotting, but no change in E-cadherin, intercell ular adhesion molecule-1, or CD44 was observed in RA-treated Colo 201 cells. Although the adhesion of Colo 201 cells to ECM, depends on the Arg-Gly-Asp sequence, levels of integrins, alpha(2), alpha(3), alpha(5 ), alpha(v), and beta(1) in differentiated adherent cells were similar to those in untreated cells. In contrast to equivalent amounts of cel l surface adhesion molecules before and after differentiation, intrace llular focal adhesion kinase (FAK) was markedly induced during KA trea tment, and the increase in FAK resulted in elevation of tyrosine-phosp horylated FAK. These findings suggest a role for FAK in activation of cell adhesion of RA-induced differentiation of these colon cancer cell s. This may serve as an appropriate model to examine the mode of activ ation of the adhesive capacity of cancer cells.