Malignant melanoma is a life-threatening skin cancer and its incidence in Caucasian populations has increased faster than any other malignancy during the last 20 years. Patients with melanoma which has spread to other organs can only survive for 6-8.5 months on average. However, the underlying molecular mechanisms that regulate the progression of melanoma are still poorly understood. We have recently found that the tumor suppressor ING4 (inhibition of growth 4) is reduced in human melanomas. We have also shown that ING4 inhibits the blood vessel formation of melanoma by inhibiting the cytokine interleukin-6 (IL-6) which helps in the recruitment of blood vessel cells to the tumor. In this proposal, we will investigate the molecular mechanism(s) through which ING4 suppresses IL-6 expression and blood vessel formation in melanoma, and thus inhibits tumor growth and spread to other organs. We will also restore ING4 in tumors to see if this will inhibit melanoma growth and tumor spread. Hence, this study will provide the essential information for designing novel therapeutic strategies for human melanoma.