Researchers involved
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Researchers involved |
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In general:
Colorectal cancer is the third most common form of cancer and the second leading
cause of cancer-related death in the Western world. The vast majority of colorectal
cancer patients die due to tumor metastases. The main goal of our research is
the elucidation of the molecular basis of colorectal tumour invasion and metastasis.
The main oncoprotein in colorectal cancer is the Wnt-pathway effector beta-catenin,
which in most cases is stabilized due to mutations in the adenomatous polyposis
coli (APC) tumor suppressor. Beta-catenin stabilization results in intracellular
accumulation and translocation into the nucleus where it associates with members
of the Tcf family of transcription factors, thus regulating the expression of
specific downstream Wnt target genes. Beta-catenin is involved in a broad spectrum
of cellular processes ranging from cell-cell adhesion to migration, differentiation,
epithelial-mesenchymal transition and self-renewal. In our research, we study
APC and beta-catenin driven tumorigenesis in several pre-clinical and in vitro
models.
Figure: Invasive structures of tumors often show a stronger nuclear staining
for beta-catenin.
Research projects:
Cross-talk between tyrosine kinases and beta-catenin signalling in colorectal
cancer:
A large number of cancers, including colorectal cancer, are characterized
by increased growth factor signalling caused by overexpression or mutational
activation of receptor tyrosine kinases (RTK) or upstream components. At various
cellular levels, beta-catenin and RTK signalling pathways show extensive cross-regulation.
One aspect of this cross-regulation is the RTK-mediated tyrosine phosphorylation
of beta-catenin resulting in its release from adherens junctions and in the
increase of its signalling pool. We study the role of tyrosine phosphorylation
of beta-catenin in intestinal tumor progression and metastasis. To this aim we use different pre-clinical models and in vitro systems
The role of growth factors produced by surrounding mesenchyme in colorectal
tumorigenesis:
Tumor cells largely depend on the surrounding tumor mesenchyme to establish
a permissive and supportive growth environment. Changes in growth factor expression
have been observed within the mesenchymal microenvironment, and can also be
detected in the neoplastic epithelial cells. These growth factors may affect
tumor growth and invasiveness in an autocrine and/or paracrine fashion. We study
the interaction between growth factors, coming from the microenvironment and
the tumor itself, and the Wnt/beta-catenin pathway on intestinal tumor progression
and metastasis.
Key publications:
