The Role of Histone Demethylase GASC1 in Cancer and its Therapeutic Potential

Interdependent genetic and epigenetic events control the initiation and progression of tumors. Genetic amplification and overexpression of the GASC1 (gene amplified in squamous cell carcinoma 1) gene has been found in various tumor types and this upregulation correlates with a poor prognosis for cancer patients. Gain- and loss-of –function approaches demonstrate the importance of GASC1 for the maintenance of cancer phenotypes. The GASC1 gene encodes a Jumonji C domain-containing protein, a newly identified histone lysine demethylase, that mainly catalyzes demethylation of tri- and di-methylated forms of histone H3 lysine 9 (H3K9me3/me2) epigenetic repressive marks. Recent studies indicated that over-production of GASC1 may induce alterations in epigenetic histone methylation and affects the expression of key genes that are implicated in carcinogenesis and stem cell properties in human cancer. Furthermore, histone demethylases, such as GASC1, represent highly promising anti-cancer therapeutic targets; a number of GASC1 inhibitors have been identified and reported. This review provides an overview of the current findings on genetic alterations and the biological function of GASC1 in cancer, together with a summary of recent advances in GASC1 inhibitor discovery.