The effects of modifying RhoA and Rac1 activities on heterotypic contact inhibition of locomotion

Contact inhibition of locomotion (CIL) occurs when a cell ceases moving in the same direction following contact with another cell. Homotypic and heterotypic CIL occur between cells of the same and different types, respectively. Using Abercrombie’s confronted explants assay we studied the effect of changing Rac1 or RhoA activities on heterotypic CIL between NIH3T3 and chicken heart fibroblasts. Both dominant active (L61) and dominant negative (N17) Rac1 expressed in NIH3T3 cells resulted in loss of heterotypic CIL. N17Rac1 expression caused RhoA activation. Increasing RhoA activity directly (V14RhoA) or indirectly (downregulation of N-cadherin or p120-catenin) also resulted in loss of CIL. High RhoA activity has been associated with tumour invasion and our results are consistent with loss of heterotypic CIL playing a role.

► Dominant active or negative Rac1 cause a loss of het CIL.
► Constitutively active V14RhoA causes a loss of het CIL.
► Defective hetCIL caused by dominant negative Rac1 is due to RhoA activation.
► Down regulation of N-cadherin or p120 catenin results in loss of het CIL.
► A fine balance between Rac1 and RhoA activities is required for het CIL.