Calretinin mediates apoptosis in small cell lung cancer cells expressing tetraspanin CD9

A majority of small cell lung cancer (SCLC) cells lack a metastasis suppressor, tetraspanin CD9, and CD9 expression promotes their apoptosis. By a proteomics‐based approach, we compared an SCLC cell line with its CD9 transfectant and found that a calcium‐binding neuronal protein, calretinin, is upregulated in CD9‐positive SCLC cells. Ectopic or anticancer drug‐induced CD9 expression upregulated calretinin, whereas CD9 knockdown down‐regulated calretinin in SCLC cells. When calretinin was knocked down, CD9‐positive SCLC cells revealed increased Akt phosphorylation and decreased apoptosis. These results suggest that CD9 positively regulates the expression of calretinin that mediates proapoptotic effect in SCLC cells.