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Wobus, Manja; Huber, Otmar; Hamann, Jörg; Aust, Gabriela

CD97 overexpression in tumor cells at the invasion front in colorectal cancer (CC) is independently regulated of the canonical Wnt pathway

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  • Medientyp: E-Artikel
  • Titel: CD97 overexpression in tumor cells at the invasion front in colorectal cancer (CC) is independently regulated of the canonical Wnt pathway
  • Beteiligte: Wobus, Manja; Huber, Otmar; Hamann, Jörg; Aust, Gabriela
  • Erschienen: Wiley, 2006
  • Erschienen in: Molecular Carcinogenesis
  • Sprache: Englisch
  • DOI: 10.1002/mc.20262
  • ISSN: 0899-1987; 1098-2744
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Invasion of colorectal carcinomas (CC) is characterized by nuclear accumulation of β‐catenin, a key component of the Wnt pathway, in scattered tumor cells. β‐catenin acts in cooperation with T‐cell factor (Tcf) HMG‐box transcription factors as a transcriptional activator of genes involved in tumor progression. Overexpression of CD97, a molecule that correlates with dedifferentiation and tumor stage in CC, parallels to nuclear translocation of β‐catenin. Here, we investigated whether CD97 is a direct β‐catenin/Tcf target gene. SW480 CC cells were used to mimic the phenotypical switch between central and invasive tumor areas. We demonstrate two‐fold higher CD97 expression and nuclear β‐catenin accumulation in cells grown at low density compared to cells cultured at high density, showing membrane‐associated β‐catenin. This suggests that CD97 expression correlates with the cellular localization of β‐catenin. However, CD97 mRNA expression levels were not affected by Tcf‐1 or Tcf‐4 as determined in inducible dominant‐negative (dn) Tcf CC cell lines. Furthermore, co‐expression of wildtype (wt) or S33A mutated β‐catenin with Tcf‐4 did not influence <jats:italic>CD97</jats:italic> promoter activity. Inhibition of glycogen synthase kinase (GSK)‐3β, a negative regulator of the canonical Wnt pathway, had no influence on CD97 expression levels. In summary, enhanced CD97 expression in CC cells is regulated independent of β‐catenin/Tcf‐4, and is thus not a direct target of the canonical Wnt pathway. © 2006 Wiley‐Liss, Inc.</jats:p>