β-Catenin activates a coordinated expression of the proinvasive factors laminin-5 γ2 chain and MT1-MMP in colorectal carcinomas
✍ Scribed by Falk Hlubek; Simone Spaderna; Andreas Jung; Thomas Kirchner; Thomas Brabletz
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- French
- Weight
- 309 KB
- Volume
- 108
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
In colorectal carcinomas, loss‐of‐function mutations of the adenomatous polyposis coli (APC) tumor suppressor gene lead to a nuclear accumulation of the oncogenic transcriptional activator β‐catenin, predominantly at the invasive front within the tumor host interface. Various identified genes activated by β‐catenin are associated with tumor invasion. One prerequisite for malignant tumor invasion is the ability of tumor cells to migrate. We recently described the γ2 chain of laminin as another β‐catenin target gene. Fragments of the laminin γ2 chain, resulting from cleavage by the membrane type 1 matrix metalloproteinase (MT1‐MMP), are strong inducers of epithelial cell migration. We here show a coordinated expression of nuclear β‐catenin, its target gene and MT1‐MMP substrate laminin γ2 chain, as well as MT1‐MMP in tumor cells at invasive regions of colorectal carcinomas. We further demonstrate that MT1‐MMP expression is regulated by β‐catenin/TCF through a TCF binding site in its promoter. These results suggest that nuclear β‐catenin activates the coordinated expression of the interacting proinvasive proteins laminin γ2 chain and MT1‐MMP, thereby leading to a promigratory activity at the invasive front of colorectal cancers. This further supports an important role of β‐catenin for invasion and metastasis of colorectal carcinomas. © 2003 Wiley‐Liss, Inc.