Characterization of Tid1, a mammalian homologue of Drosophila tumor suppressor Tid56, in oral cancer tumorigenesis

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA 1789 Head and neck squamous cell carcinoma (HNSCC), including oral cancer, is the sixth most prevalent malignancy cancer worldwide. In Taiwan, oral cancer is the 4th leading cancer that causes mortality in male. This malignant disease can’t be well controlled because of the lack of understanding of the molecular mechanism by which renders oral cancer tumorigenesis, as well as the diagnosis for early detection or therapeutic treatments. It is warrant to identify the oral cancer associated genes, and the functions of these genes in tumorigenesis. The human tumorous imaginal disc 1 (Tid1 or DnaJa3) is a member of the DnaJ domain proteins family, which is involved in multiple intracellular signaling pathways such as stress induced apoptosis, cell proliferation or cell survival. Previous studies have demonstrated that Tid1 is involved in human carcinogenesis. However, how does the molecular mechanism mediated by Tid1 play a role in oral cancer tumorigenesis is poorly understood. In this study, tissue samples from clinical oral cancer patients were collected to evaluate the expression level of Tid1 through immunohistochemistry analysis. Significant loss or decrease of Tid1 positive staining was observed in late-stage oral tumor tissues. Expression level of Tid1 was also negatively associated with tumor status, recurrence, and patient survival suggesting that Tid1 may participate in the mechanism of tumor development. To further identify the function of Tid1 in oral cancer cells in vitro , we ectopically overexpressed Tid1 in oral cancer cell line of downergulated Tid1. Restoration of Tid1 significantly inhibited the capability of cell proliferation, migration, invasion and anchorage-independent growth in Tid1 overexpressed cells. Conversely, depletion of Tid1 in oral cancer cells by RNA interference enhanced cell proliferation, cell migration and cell invasion of Tid1 depleted cells, and also protected these cells from stress induced apoptosis. In conclusion, we identified that Tid1 was differentially expression in oral cancer tissue. Additionally, Tid1 functioned as a tumor suppressor through studies generated from oral cancer cells in vitro.