COLO 201

MUC1-C Suppresses MICA Expression by Human Cancer Cells

MUC1-C evolved to protect barrier tissues but promotes oncogenesis and T cell dysfunction in cancers. Its role in NK cell function is unknown. Morimoto et al. investigated how MUC1-C affects NK cell-activating MICA/B ligands and explores mechanisms of immune evasion in cancer.

To test whether MUC1-C has a role in innate NK cell immunity, we assessed its impact on the expression of NKG2D ligands. RNA-seq data revealed that silencing MUC1-C significantly upregulated MICA and MICB transcripts in human colorectal cancer (RKO, COLO 201), triple-negative breast cancer (BT-549), non-small cell lung cancer (H1975), and castration-resistant prostate cancer (DU-145) cells (Fig. 1A). Silencing MUC1-C also increased ULBP3, ULBP6/RAET1L, and CD48 expression, though the effects on ULBP ligands varied across cancer types (Fig. 1A). They focused on MICA and confirmed that silencing MUC1-C induced MICA expression in RKO (Fig. 1B) and COLO 201 cells (Fig. 1C). Similar results were seen with a second MUC1 shRNA. MUC1-C was also required for MICA expression in BT-549 (Fig. 1D), H1975, and DU-145 cells (online supplemental figure S1C). Flow cytometry analyses showed that MUC1 silencing led to increased cell surface MICA in RKO (Fig. 1E) and COLO 201 cells (Fig. 1F) and yielded similar results in BT-549 (Fig. 1G), H1975, and DU-145 cells. Taken together, MUC1-C represses MICA gene and cell surface expression in a wide range of cancer cells.