The role of Nodal and Cripto‐1 in human oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a common epithelial malignancy of the oral cavity. Nodal and Cripto‐1 (CR‐1) are important developmental morphogens expressed in several adult cancers and are associated with disease progression. Whether Nodal and CR‐1 are simultaneously expressed in the same tumor and how this affects cancer biology are unclear. We investigate the expression and potential role of both Nodal and CR‐1 in human OSCC. Immunohistochemistry results show that Nodal and CR‐1 are both expressed in the same human OSCC sample and that intensity of Nodal staining is correlated with advanced‐stage disease. However, this was not observed with CR‐1 staining. Western blot analysis of lysates from two human OSCC line experiments shows expression of CR‐1 and Nodal, and their respective signaling molecules, Src and ERK1/2. Treatment of SCC25 and SCC15 cells with both Nodal and CR‐1 inhibitors simultaneously resulted in reduced cell viability and reduced levels of P‐Src and P‐ERK1/2. Further investigation showed that the combination treatment with both Nodal and CR‐1 inhibitors was capable of reducing invasiveness of SCC25 cells. Our results show a possible role for Nodal/CR‐1 function during progression of human OSCC and that targeting both proteins simultaneously may have therapeutic potential.