Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling

Dow, L. E., Elsum, I. A., King, C. L., Kinross, K. M., Richardson, H. E., Humbert, P. O. (2008) Loss of human Scribble cooperates with H-Ras to promote cell invasion through deregulation of MAPK signalling. Oncogene, 27 (46). pp. 5988-6001.

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URL: https://www.ncbi.nlm.nih.gov/pubmed/18641685
DOI: 10.1038/onc.2008.219

Abstract

Activating mutations in genes of the Ras-mitogen-activated protein kinase (MAPK) pathway occur in approximately 30% of all human cancers; however, mutation of Ras alone is rarely sufficient to induce tumour development. Scribble is a polarity regulator recently isolated from a Drosophila screen for events that cooperate with Ras mutation to promote tumour progression and cell invasion. In mammals, Scribble regulates directed cell migration and wound healing in vivo; however, no role has been identified for mammalian Scribble in oncogenic transformation. Here we show that in human epithelial cells expressing oncogenic Ras or Raf, loss of Scribble promotes invasion of cells through extracellular matrix in an organotypic culture system. Further, we show that the mechanism by which this occurs is in the regulation of MAPK signalling by Scribble. The suppression of MAPK signalling is a highly conserved function of Scribble as it also prevents Raf-mediated defects in Drosophila wing development. Our data identify Scribble as an important mediator of MAPK signalling and provide a molecular basis for the observation that Scribble expression is decreased in many invasive human cancers. © 2008 Macmillan Publishers Limited All rights reserved.

Item Type: Paper
Uncontrolled Keywords: Cancer Invasion Ras Scribble
Subjects: diseases & disorders > cancer
organism description > animal > insect > Drosophila
bioinformatics > genomics and proteomics > analysis and processing > NETBAG
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Tom Adams
Date: 2008
Date Deposited: 25 Aug 2011 16:03
Last Modified: 13 Mar 2018 20:39
Related URLs:
URI: http://repository.cshl.edu/id/eprint/7720

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