Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.

Published

Journal Article

Despite extensive effort, there has been limited progress in the development of direct RAS inhibitors. Targeting isoprenylcysteine carboxylmethyltransferase (ICMT), a unique enzyme of RAS post-translational modification, represents a promising strategy to inhibit RAS function. However, there lacks direct genetic evidence on the role of ICMT in RAS-driven human cancer initiation and maintenance. Using CRISPR/Cas9 genome editing, we have created Icmt loss-of-function isogenic cell lines for both RAS-transformed human mammary epithelial cells (HME1) and human cancer cell lines MiaPaca-2 and MDA-MB-231 containing naturally occurring mutant KRAS. In both in vitro and in vivo tumorigenesis studies, Icmt loss-of-function abolishes the tumor initiation ability of all major isoforms of mutant RAS in HME1 cells, and the tumor maintenance capacity of MiaPaca-2 and MDA-MB-231 cells, establishing the critical role of ICMT in RAS-driven cancers.

Full Text

Duke Authors

Cited Authors

  • Lau, HY; Tang, J; Casey, PJ; Wang, M

Published Date

  • July 6, 2017

Published In

Volume / Issue

  • 36 / 27

Start / End Page

  • 3934 - 3942

PubMed ID

  • 28192404

Pubmed Central ID

  • 28192404

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

Digital Object Identifier (DOI)

  • 10.1038/onc.2016.508

Language

  • eng

Conference Location

  • England