STUDY OF ISOPRENYLCYSTEINE CARBOXYLMETHYLTRANSFERASE SUPPRESSION IN CANCER

Abstract

DNA damage response is a well-known cellular events playing an important role in maintaining genomic stability and cell survival. Dysregulation of this process results in many diseases. Recently, it has drawn attention that DNA damage response plays a dynamic role in cancer formation and progression. Isoprenylcysteine carboxylmethyltransferase (ICMT) is the unique enzyme for the last step of the prenylation process of CaaXmotif containing proteins, which include many oncogenic proteins, such as RAS. Our study has found, for the first time, that targeting ICMT results in the increase of DNA damage, delay of G2/M entry, induction of cell death and reduction of tumorigenesis in many breast cancer cell lines. We also found that ICMT inhibition enhance the effect of PARPi, leading to apoptosis of breast cancer cells. These studies bring new understanding on targeting DNA damage response as cancer therapeutics.