Abstract
N‐WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N‐WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N‐WASP in the initiation and progression of colorectal cancer. While deletion of N‐wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche, and migration up the crypt–villus axis was enhanced. Loss of N‐wasp promoted adenoma formation in an adenomatous polyposis coli (Apc) deletion model of intestinal tumourigenesis. Thus, we establish a tumour suppressive role of N‐WASP in early intestinal carcinogenesis despite its later pro‐invasive role in other cancers. Our study highlights that while the actin cytoskeletal machinery promotes invasion of cancer cells, it also maintains normal epithelial tissue function and thus may have tumour suppressive roles in pre‐neoplastic tissues. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Highlights
Colorectal carcinoma (CRC) is the second most common cancer in Europe, with the second highest mortality rate [1]
N-WASP is not required for short-term homeostasis in the intestine or colon
N-WASP is expressed along the entire length of the epithelium of mouse intestine and colon and appears cytoplasmic and membrane-associated (Figure 1A, B)
Summary
Colorectal carcinoma (CRC) is the second most common cancer in Europe, with the second highest mortality rate [1]. In spite of advances in diagnosis and management resulting in overall improved prognosis for patients with CRC, survival rates remain poor for those with advanced disease at presentation [2]. Improved understanding of the pathogenesis and progression of CRC is desirable, in order to mediate early diagnosis and prevention of metastasis. Depletion of N-WASP in breast cancer cells decreased invasion and matrix remodelling [6] and led to decreased motility and metastasis [7]. N-WASP is potentially a key target for invasion and metastasis of epithelial cancers. In addition to its role in cancer, N-WASP has a scaffolding role in cell–cell adhesion and signalling in epithelial tissues. N-WASP is important for normal tissue architecture and integrity, so careful consideration must be given to whether disruption of N-WASP in cancer would have a positive or a negative effect on progression
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
