Tumour maintenance is mediated by eNOS.

Journal Article (Journal Article)

Tumour cells become addicted to the expression of initiating oncogenes like Ras, such that loss of oncogene expression in established tumours leads to tumour regression. HRas, NRas or KRas are mutated to remain in the active GTP-bound oncogenic state in many cancers. Although Ras activates several proteins to initiate human tumour growth, only PI3K, through activation of protein kinase B (PKB; also known as AKT), must remain activated by oncogenic Ras to maintain this growth. Here we show that blocking phosphorylation of the AKT substrate, endothelial nitric oxide synthase (eNOS or NOS3), inhibits tumour initiation and maintenance. Moreover, eNOS enhances the nitrosylation and activation of endogenous wild-type Ras proteins, which are required throughout tumorigenesis. We suggest that activation of the PI3K-AKT-eNOS-(wild-type) Ras pathway by oncogenic Ras in cancer cells is required to initiate and maintain tumour growth.

Full Text

Duke Authors

Cited Authors

  • Lim, K-H; Ancrile, BB; Kashatus, DF; Counter, CM

Published Date

  • April 3, 2008

Published In

Volume / Issue

  • 452 / 7187

Start / End Page

  • 646 - 649

PubMed ID

  • 18344980

Pubmed Central ID

  • PMC2688829

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

Digital Object Identifier (DOI)

  • 10.1038/nature06778


  • eng

Conference Location

  • England