Partial Depletion of SART1 Selectively Induces Mitotic Defects and Cell Death in Cancer Cells

Cancer cells proliferate uncontrollably, and a major challenge in cancer research is to identify strategies that selectively eliminate cancer cells while sparing normal cells. Squamous cell carcinoma antigen recognized by T cells 1 (SART1) was originally identified as a carcinoma-associated antigen and is frequently overexpressed in cancer cells. Recently, SART1 has been identified as a microtubule-associated protein required for spindle pole formation and cell division. Here, we show that partial depletion of SART1 by RNA interference selectively disrupts mitotic spindle assembly and induces cell death in cancer cells. siRNA-mediated knockdown reduced SART1 protein levels comparably in multiple human cell types, yet spindle defects and apoptotic cell death were observed in HeLa and U2OS cancer cells but not in non-transformed BJ fibroblasts or RPE1 epithelial cells. Consistent with this cancer-selective sensitivity, SART1 depletion markedly suppressed oncogene c-Myc-induced transformation of RPE1 cells without impairing the growth of untransformed cells. These results demonstrate that partial depletion of SART1 preferentially induces spindle defects and cell death in transformed cells. Given that complete loss of SART1 is incompatible with normal development, our findings suggest that transient or partial inhibition of SART1 may provide a basis for selectively eliminating transformed cells while sparing normal cells.