Mechanism of Receptor Tyrosine Kinase Transactivation in Skin Cancer Cell Lines

The main findings of this study are: 1. UV led to EGFR transactivation in melanoma and squamous cell carcinoma cell lines. This pathway conferred cancer cells with survival advantage under UV irradiation. 2. UV/GPCR induced EGFR transactivation was found to be dependent on ROS production by the Nox protein family. 3. Inhibition strategies targeting ADAMs led to higher apoptosis by UV irradiation as compared to the direct EGFR inhibition, which could be explained by differences in the ability of inhibitors to induce cell cycle arrest. Additionally, we demonstrated a selective presence of EGFR transactivation pathway in malignant melanoma, and absence in primary melanoma. Blocking EGFR transactivation pathway thus holds prophylactic and therapeutic potential in skin cancer.