Wnt5a promotes human colon cancer cell migration and invasion but does not augment intestinal tumorigenesis in Apc1638N mice

Autor: Martin van der Valk, Werner Helvensteijn, Sigrid M. A. Swagemakers, Patrick Franken, Asha M. Das, Elvira R M Bakker, Ernst J. Kuipers, Ron Smits, Wendy van Veelen, Timo L.M. ten Hagen
Přispěvatelé: Gastroenterology & Hepatology, Surgery, Pathology
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Genetically modified mouse
Oncology
Cancer Research
medicine.medical_specialty
Colorectal cancer
Adenomatous Polyposis Coli Protein
Blotting
Western
Apoptosis
Mice
Transgenic
Mouse model of colorectal and intestinal cancer
Biology
Real-Time Polymerase Chain Reaction
Wnt-5a Protein
Metastasis
Focal adhesion
Immunoenzyme Techniques
Mice
SDG 3 - Good Health and Well-being
Cell Movement
Internal medicine
Proto-Oncogene Proteins
medicine
Cell Adhesion
Tumor Cells
Cultured
Animals
Humans
Neoplasm Invasiveness
RNA
Messenger
Intestinal Mucosa
Cell Proliferation
Mice
Knockout
Gene knockdown
Focal Adhesions
Reverse Transcriptase Polymerase Chain Reaction
Wnt signaling pathway
Cell migration
General Medicine
medicine.disease
Intestines
Wnt Proteins
body regions
Cell Transformation
Neoplastic
Colonic Neoplasms
embryonic structures
Cancer research
sense organs
Zdroj: Carcinogenesis, 34(11), 2629-2638. Oxford University Press
ISSN: 1460-2180
0143-3334
Popis: Whereas aberrant activation of canonical Wnt/β-catenin signaling underlies the majority of colorectal cancer cases, the contribution of non-canonical Wnt signaling is unclear. As enhanced expression of the most extensively studied non-canonical Wnt ligand WNT5A is observed in various diseases including colon cancer, WNT5A is gaining attention nowadays. Numerous in vitro studies suggest modulating capacities of WNT5A on proliferation, differentiation, migration and invasion, affecting tumor and non-mutant cells. However, a possible contribution of WNT5A to colorectal cancer remains to be elucidated. We have analyzed WNT5A expression in colorectal cancer profiling data sets, altered WNT5A expression in colon cancer cells and used our inducible Wnt5a transgenic mouse model to gain more insight into the role of WNT5A in intestinal cancer. We observed that increased WNT5A expression is associated with poor prognosis of colorectal cancer patients. WNT5A knockdown in human colon cancer cells caused reduced directional migration, deregulated focal adhesion site formation and reduced invasion, whereas Wnt5a administration promoted the directional migration of colon cancer cells. Despite these observed protumorigenic activities of WNT5A, the induction of Wnt5a expression in intestinal tumors of Apc1638N mice was not sufficient to augment malignancy or metastasis by itself. In conclusion, WNT5A promotes adhesion sites to form in a focal fashion and promotes the directional migration and invasion of colon cancer cells. Although these activities appear insufficient by themselves to augment malignancy or metastasis in Apc1638N mice, they might explain the poor colon cancer prognosis associated with enhanced WNT5A expression.
Databáze: OpenAIRE
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