Notch-4 contributes to the metastasis of salivary adenoid cystic carcinoma.

The Notch signaling pathway is important for cell-cell communication; it is involved in gene regulation mechanisms that control multiple cell differentiation processes during embryonic and adult life. Notch is present in all metazoans, and vertebrates possess four different Notch receptors: Notch-1, Notch-2, Notch-3, and Notch-4. The aim of the present study was to identify the role of Notch protein in the metastasis of salivary adenoid cystic carcinoma (SACC). Real-time PCR results showed that Notch-1, Notch-2, and Notch-4 were upregulated in the highly metastatic SACC cell line ACC-M, compared to ACC-2, a SACC cell line with low metastatic ability. Knockdown of Notch-4 by small interfering RNA efficiently inhibited the invasion of ACC-M cells. Notch-4 expression was significantly higher in the clinical samples with metastasis and recurrence compared to that in control (p<0.05), shown by immunohistochemistry analysis. These results indicate that Notch-4 may play an important role in SACC metastasis.