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

Publication ,  Journal Article
Lau, HY; Tang, J; Casey, PJ; Wang, M
Published in: Oncogene
July 6, 2017

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.

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Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

July 6, 2017

Volume

36

Issue

27

Start / End Page

3934 / 3942

Location

England

Related Subject Headings

  • ras Proteins
  • Xenograft Model Antitumor Assays
  • Tamoxifen
  • Protein Methyltransferases
  • Protein Isoforms
  • Oncology & Carcinogenesis
  • Mutation, Missense
  • Mice, SCID
  • Humans
  • Cell Transformation, Neoplastic
 

Citation

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Lau, H. Y., Tang, J., Casey, P. J., & Wang, M. (2017). Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms. Oncogene, 36(27), 3934–3942. https://doi.org/10.1038/onc.2016.508
Lau, H. Y., J. Tang, P. J. Casey, and M. Wang. “Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.Oncogene 36, no. 27 (July 6, 2017): 3934–42. https://doi.org/10.1038/onc.2016.508.
Lau, H. Y., et al. “Isoprenylcysteine carboxylmethyltransferase is critical for malignant transformation and tumor maintenance by all RAS isoforms.Oncogene, vol. 36, no. 27, July 2017, pp. 3934–42. Pubmed, doi:10.1038/onc.2016.508.

Published In

Oncogene

DOI

EISSN

1476-5594

Publication Date

July 6, 2017

Volume

36

Issue

27

Start / End Page

3934 / 3942

Location

England

Related Subject Headings

  • ras Proteins
  • Xenograft Model Antitumor Assays
  • Tamoxifen
  • Protein Methyltransferases
  • Protein Isoforms
  • Oncology & Carcinogenesis
  • Mutation, Missense
  • Mice, SCID
  • Humans
  • Cell Transformation, Neoplastic