Grant: Project Grant

Squamous cell carcinoma (SCC) is one of the most prevalent types of malignancy and its incidence continues to increase globally. The fatal consequences of cancer are due to the spreading (metastasis) of cancer cells from the original tumor site to other organs of the body. Despite intensive research efforts, there has been limited success in blocking recurrence and metastasis that occurs in a significant proportion of these patients. Transforming growth factor beta (TGF-beta) is a growth factor that is important for normal development and maintenance of healthy tissues. TGF-beta normally acts as a tumor suppressor by inhibiting the growth of cells but switches to a tumor promoter during cancer progression by making cells more invasive and metastatic. We have identified a cell surface protein named CD109 and found that it acts as a strong inhibitor of TGF-beta actions. Emerging evidence indicates that CD109 levels are increased in skin and oral SCC, and premalignant lesions in the oral cavity that highly express CD109 show a greater risk to progress to SCC. In addition, studies indicate that CD109 not only inhibits TGF-beta but may also activate other tumor promoting (oncogenic) pathways including those initiated by proteins known as EGFR and Jak/Stat3. The proposed research will determine whether CD109 promotes skin and oral SCC progression and metastasis in experimental models and establish the mechanisms that mediate the CD109's actions. The findings from the proposed studies is anticipated to lead to the development of novel CD109-based molecules for the treatment of skin and oral SCC.