Effect of N-Wasp knockout on tumour burden and survival in murine models of intestinal tumorigenesis and its potential as a prognostic biomarker in human colorectal cancer

Abstract Background APC loss is a common initiating event in colorectal cancer but additional mutations are required for progression along the adenoma–carcinoma pathway. The Neural Wiskott–Aldrich syndrome protein (N-WASP) is crucial for invasion in a variety of cancers. Its role in colorectal cance...

Full description

Saved in:
Bibliographic Details
Published in:The Lancet (British edition) 2017-02, Vol.389, p.S71-S71
Main Authors: Morris, Hayley T, Dr, Fort, Loic, MSc, Ridgway, Rachael A, PhD, Sansom, Owen J, PhD, Carey, Francis A, MD, Machesky, Laura M, PhD
Format: Article
Language:English
Subjects:
Internal Medicine
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background APC loss is a common initiating event in colorectal cancer but additional mutations are required for progression along the adenoma–carcinoma pathway. The Neural Wiskott–Aldrich syndrome protein (N-WASP) is crucial for invasion in a variety of cancers. Its role in colorectal cancer has not been investigated; however, it is implicated in Wnt signalling (the pathway affected when APC function is lost). The aim of this project was to investigate the role of N-WASP in intestinal tumorigenesis and its potential as a prognostic biomarker. Methods The effect of N-Wasp knockout (N-Waspfl/fl) on survival and tumour burden was investigated using two established murine models of intestinal tumorigenesis (Apcfl/+ and Apcfl/+ KrasG12D/+). Immunohistochemistry for N-WASP was performed on two human tissue microarrays—namely, colorectal cancers with linked clinicopathological data and long-term follow-up, and early cancers diagnosed via bowel screening. N-WASP expression was assessed by weighted histoscore, and correlation with survival was tested. Findings N-Wasp knockout decreased survival in the Apcfl/+ model (median survival 143 days [IQR 127·3–167·0] vs 269 [228·8–304·5], p
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(17)30467-1