Two opposite effects of desmoglein 3 on the growth of oral squamous cell carcinoma between anchorage -dependent and -independent conditions
Desmoglein 3 (Dsg3) is one of the desmosomal cadherins. Recent studies have reported that Dsg3 is abnormally expressed in oral squamous cell carcinoma (OSCC) and associated with tumor growth and poor survival. A role of Dsg3 in the progression of OSCC remains controversial, since both positive and negative effect on the cancer progression have been reported. Previously we have demonstrated that OSCC cells from the metastatic lymph nodes showed significantly higher DSG3 expression compared to those from the primary tumor of the same patients. Here we investigated the effect of Dsg3 expression on the growth of OSCC between anchorage-dependent (AD) and -independent (AID) conditions. Cell lines established from the primary tumor (P) and metastatic lymph nodes (LY) of three OSCC patients and two commercial OSCC cell lines were used for the experiments. Under AD conditions, Dsg3-low cell lines (Dsg3-low) had higher cell proliferation and migration ability than Dsg3-high cell lines (Dsg3-high) of the same patients. After transferred into AID conditions, all the cell lines except Dsg3-negative 7P showed increased Dsg3 expression by up to 50-fold, compared with AD conditions. Under AID conditions, all the patients showed higher cell proliferation ability in the Dsg3-high compared with Dsg3-low, which was marked contrast to AD conditions. Dsg3 knockdown under AD conditions increased the cell proliferation rate of all the cell lines except Dsg3-negative line. On the other hand, cell growth was not affected under AID conditions. These results suggested that Dsg3 may have two opposite effects on the growth of OSCC cells between AD and AID conditions, and that the involvement of molecules other than Dsg3 may also be important. Therefore, we investigated DEGs by Dsg3 knockdown under AD and AID conditions and their functions. Overall design: To investigate the differences in DSG3 function and DEGs on anchorage conditions, OSCC cell lines were cultured under AD and AID conditions, and DSG3 was knocked down by siRNA DEGs were extracted when Dsg3-positive cells were knocked down.  Gene otology (GO) analysis was performed to identify the functional annotations of the extracted DEGs.