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  • Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression.

Down-regulation of the homeodomain factor Cdx2 in colorectal cancer by collagen type I: an active role for the tumor environment in malignant tumor progression.

Cancer research (2004-10-07)
Thomas Brabletz, Simone Spaderna, Jochen Kolb, Falk Hlubek, Gerhard Faller, Christiane J Bruns, Andreas Jung, Jens Nentwich, Isabelle Duluc, Claire Domon-Dell, Thomas Kirchner, Jean-Noel Freund
ABSTRACT

The homeobox transcription factor Cdx2 specifies intestinal development and homeostasis and is considered a tumor suppressor in colorectal carcinogenesis. However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is characterized by a transient loss of differentiation and nuclear accumulation of the oncoprotein beta-catenin in budding tumor cells. Strikingly, this is reversed in growing metastases, indicating that tumor progression is a dynamic process that is not only driven by genetic alterations but also regulated by the tumor environment. Here we describe a transient loss of Cdx2 in budding tumor cells at the tumor host interface, and reexpression of Cdx2 in metastases. Cell culture experiments show that collagen type I, through beta(1) integrin signaling, triggers a transient transcriptional down-regulation of Cdx2 and its intestine-specific target gene sucrase isomaltase, associated with a loss of differentiation. These data indicate an active role for the tumor environment in malignant tumor progression.

MATERIALS
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Product Description

Sigma-Aldrich
Monoclonal Anti-Cytokeratin Peptide 18 antibody produced in mouse, clone CY-90, ascites fluid