Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/136599
Title: ELUCIDATING THE FUNCTION OF ISOPRENYLCYSTEINE CARBOXYLMETHYLTRANSFERASE (ICMT) IN CANCER
Authors: LAU HIU YEUNG
Keywords: Icmt, mutant Ras, tumorigenesis, CRISPR, cancer therapy, compound 8.12
Issue Date: 5-Jun-2017
Citation: LAU HIU YEUNG (2017-06-05). ELUCIDATING THE FUNCTION OF ISOPRENYLCYSTEINE CARBOXYLMETHYLTRANSFERASE (ICMT) IN CANCER. ScholarBank@NUS Repository.
Abstract: Isoprenylcysteine carboxylmethyltransferase (Icmt), the enzyme catalyzing the last step of the prenylation pathway for proteins with C-terminal CaaX-motifs such as Ras, has been investigated for its potential to be developed as a target for cancer therapy, especially for mutant Ras-driven cancers. We report the biological effects of a novel Icmt inhibitor, Compound 8.12. Compound 8.12 treatment was found to result in the display of the hallmarks of Icmt inactivation in cells, improved reduction in cancer cell viability and xenograft tumor formation compared to the prototypical indole-based Icmt inhibitor, cysmethynil. To further ascertain the role of Icmt in cancer initiation and maintenance, we created Icmt loss-of-function cell lines using CRISPR/Cas9 technology. Icmt loss-of-function was found to significantly attenuate the transforming ability of all isoforms of mutant-Ras in pre-malignant HMECs, as well as significantly reducing the ability of cancer cell lines harboring activating K-Ras mutations to form tumors in mice.
URI: http://scholarbank.nus.edu.sg/handle/10635/136599
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
LauHY.pdf10.36 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

102
checked on Dec 1, 2022

Download(s)

19
checked on Dec 1, 2022

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.