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Heterogeneous expression of Wnt/β‐catenin target genes within colorectal cancer
Author(s) -
Hlubek Falk,
Brabletz Thomas,
Budczies Jan,
Pfeiffer Sabine,
Jung Andreas,
Kirchner Thomas
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22916
Subject(s) - wnt signaling pathway , biology , catenin , colorectal cancer , tumor progression , cancer research , extracellular matrix , gene expression profiling , mouse model of colorectal and intestinal cancer , tumor suppressor gene , gene expression , pathology , cancer , carcinogenesis , gene , microbiology and biotechnology , medicine , genetics
Invasion of common colorectal adenocarcinomas is coupled with a transient loss of epithelial differentiation of tumor cells. Previously, we have shown that dedifferentiated tumor cells at the invasive front (IF) accumulate the transcriptional activator β‐catenin in the nucleus, in contrast to cells of the tumor center. To characterize the cells of these two morphogenic tumor areas, gene expression profiling was performed. Our study demonstrates that intratumorous heterogeneity in colorectal cancer correlates with differential expression of 510 genes between the central tumor region (TC) and the IF. Many genes differentially expressed at the IF are involved in cellular invasion processes like cell motility, cell adhesion and extracellular matrix interaction. This in vivo analysis shows overexpression of known Wnt/β‐catenin target genes either in the entire tumor tissue (compared to normal mucosa) or specifically at the IF. Thus, even though all tumor cells overexpress β‐catenin, the existence of at least 2 groups of Wnt/β‐catenin target genes selectively activated in different tumor regions is suggested. The concomitant high expression of inflammation‐ and tissue repair‐related genes at the IF supports the hypothesis that an inflammation‐activated microenvironment may trigger selective Wnt/β‐catenin target gene expression and contribute to the malignant progression of colorectal cancer. © 2007 Wiley‐Liss, Inc.