Activating SRC mutation in a subset of advanced human colon cancers

Rosalyn Irby, Weiguang Mao, Domenico Coppola, Jimmy Kang, Jean Marc Loubeau, Walter Trudeau, Richard Karl, Donald J. Fujita, Richard Jove, Timothy J. Yeatman

Research output: Contribution to journalArticlepeer-review

426 Scopus citations

Abstract

The discovery of Rous sarcoma virus (RSV) led to the identification of cellular Src (c-Src), a non-receptor tyrosine kinase, which has since been implicated in the development of numerous human cancers. c-Src has been found to be highly activated in colon cancers, particularly in those metastatic to the liver. Studies of the mechanism of c-Src regulation have suggested that c-Src kinase activity is downregulated by phosphorylation of a critical carboxy-terminal tyrosine (Tyr 530 in human c-Src, equivalent to Tyr 527 in chicken Src) and have implied the existence of activating mutations in this C-terminal regulatory region. We report here the identification of a truncating mutation in SRC at codon 531 in 12% of cases of advanced human colon cancer tested and demonstrate that the mutation is activating, transforming, tumorigenic and promotes metastasis. These results provide, for the first time, genetic evidence that activating SRC mutations may have a role in the malignant progression of human colon cancer.

Original languageEnglish (US)
Pages (from-to)187-190
Number of pages4
JournalNature Genetics
Volume21
Issue number2
DOIs
StatePublished - Feb 1999

All Science Journal Classification (ASJC) codes

  • Genetics

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