Grant: Operating Grant

Cutaneous malignant melanoma is a life-threatening skin cancer due to its high metastatic potential. The mechanism behind the high invasive property and metastatic potential of melanoma is still incompletely understood. The novel tumor suppressor ING3 has been shown to modulate gene transcription, cell cycle control, and programmed cell death. We have recently demonstrated that the nuclear ING3 expression is remarkably reduced in malignant melanoma and correlated with the progression from dysplastic nevi to primary and metastastic melanoma. This aberrant nuclear ING3 expression is also correlated with a poorer disease-specific 5-year survival of patients with primary melanoma. In this project, we will continue to delineate the molecular mechanisms controlling aberrant ING3 expression and subcellular localization and the consequent effect on ING3 tumor suppressive function in melanoma development. This project will provide in depth mechanism of ING3 deregulation in melanoma and confirm the tumor suppressive roles of ING3 in vitro and in vivo. Understanding the molecular mechanisms of controlling ING3 and its tumor suppressive functions will help us to design novel strategies for cancer prevention and treatment.