Down-Regulation of the Homeodomain Factor Cdx2 in Colorectal Cancer by Collagen Type I - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Cancer Research Année : 2004

Down-Regulation of the Homeodomain Factor Cdx2 in Colorectal Cancer by Collagen Type I

Thomas Brabletz
  • Fonction : Auteur
Simone Spaderna
  • Fonction : Auteur
Jochen Kolb
  • Fonction : Auteur
Falk Hlubek
  • Fonction : Auteur
Gerhard Faller
  • Fonction : Auteur
Christiane Bruns
  • Fonction : Auteur
Andreas Jung
  • Fonction : Auteur
Jens Nentwich
  • Fonction : Auteur
Isabelle Duluc
  • Fonction : Auteur
Claire Domon-Dell
  • Fonction : Auteur
Thomas Kirchner
  • Fonction : Auteur

Résumé

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 β-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 β1 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.

Domaines

Cancer
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Dates et versions

hal-03813556 , version 1 (13-10-2022)

Identifiants

Citer

Thomas Brabletz, Simone Spaderna, Jochen Kolb, Falk Hlubek, Gerhard Faller, et al.. Down-Regulation of the Homeodomain Factor Cdx2 in Colorectal Cancer by Collagen Type I. Cancer Research, 2004, 64 (19), pp.6973-6977. ⟨10.1158/0008-5472.CAN-04-1132⟩. ⟨hal-03813556⟩
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