Slc44a2 deletion alters tetraspanin and N-cadherin expression: Reduced adhesion and enhanced proliferation in...

Slc44a2 is reported to interact with tetraspanins CD9 and CD81. To investigate how Slc44a2 affects adhesion protein expression, cells from wild-type (WT) Slc44a2+/+, heterozygous (HET) Slc44a2+/-, and knockout (KO) Slc44a2-/- mice were cultured from lung tissue. The cultured cells expressed vimentin, N-cadherin, p120 catenin, beta-catenin, actin, CD9, and CD81, but not E-cadherin. Vimentin expression with lack of E-cadherin indicated that the cultured cells were of mesenchymal origin. Slc44a2 KO cells and HET cells demonstrated lower adherence and faster proliferation than the WT cells. All three groups displayed dramatically altered intracellular distribution of N-cadherin, CD9, and CD81. The CD9 membrane foci observed in WT cell membranes were less frequent and diminished in size in HET cells and KO cells. N-cadherin was dispersed throughout both the cytoplasm and membrane in WT cells, with similar yet weaker distribution in HET cells; however, in KO cells, N-cadherin was densely aggregated in the perinuclear cytoplasm. CD81 had a distribution pattern in WT, HET, and KO cells similar to that of N-cadherin with dense cytoplasmic clusters in the cells. KO cells also exhibited reduced filamentous actin as compared to WT cells. These results suggest that Slc44a2 is necessary for proper cellular localization of adhesion proteins and growth regulation that may be related to altered adhesion signals.