The intestine-specific homeobox gene Cdx2 decreases mobility and antagonizes dissemination of colon cancer cells

• Published in: Oncogene Vol. 27; no. 1; pp. 107 - 115
• Main Authors: Gross, I, Duluc, I, Benameur, T, Calon, A, Martin, E, Brabletz, T, Kedinger, M, Domon-Dell, C, Freund, J-N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.01.2008; Nature Publishing; Nature Publishing Group; Nature Publishing Group [1987-....]
• Subjects: Animals; Apoptosis; Biological and medical sciences; Caco-2 Cells; Cancer; Cancer cells; CDX2 Transcription Factor; Cell adhesion & migration; Cell Biology; Cell migration; Cell Migration Inhibition; Cell Movement - genetics; Cell Movement - physiology; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; DNA binding proteins; Fundamental and applied biological sciences. Psychology; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Genetic aspects; Genetics; Genotype & phenotype; Homeodomain Proteins - antagonists & inhibitors; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; HT29 Cells; Human Genetics; Humans; Internal Medicine; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Life Sciences; Male; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Nude; Molecular and cellular biology; Neoplasm Invasiveness - prevention & control; Neoplasm Metastasis - genetics; Neoplasm Metastasis - pathology; Neoplasm Metastasis - prevention & control; Oncology; original-article; Physiological aspects; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Wound Healing - genetics; Wound Healing - physiology; France; migration; wound healing; metastasis; Cdx; colon cancer; Migration; Mobility; Malignant tumor; Metastasis; Carcinogenesis; Wound; Colonic disease; Colon cancer; Dissemination; Homeotic gene; Digestive diseases; Intestinal disease; Cicatrization; Cancer
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1210601

The gravity of colorectal cancer is mainly due to the capacity of tumor cells to migrate out of the tumor mass to invade the stroma and disseminate as metastases. The acquisition of a migratory phenotype also occurs during wound healing. Here, we show that several features characterizing invasive colon tumor cells are shared by migrating cells during wound repair in vitro . In particular, the expression of the intestine-specific transcription factor Cdx2 , a key gene for intestinal identity downregulated in invasive cancer cells, is reduced during wound healing in vitro . Transcription factors involved in epithelial–mesenchymal transition such as Snail and Slug are upregulated during wound healing and are able to repress Cdx2 transcription. In vitro , forced expression of Cdx2 in human colon cancer cell lines retarded wound repair and reduced migration, whereas inhibition of Cdx2 expression by RNA interference enhanced migration. In vivo , forced expression of Cdx2 opposed tumor cells spreading in nude mice xenografted at three different sites. These data provide evidence that Cdx2 antagonizes the process of tumor cell dissemination, and they suggest that this homeobox gene might represent a new therapeutic target against metastatic spreading of colon cancer.