FOR 2438 – Cell Plasticity in Colorectal Carcinogenesis

For the development of colorectal cancer (CRC) cell-autonomous events alone are insufficient. Accumulating epidemiological, genetic and preclinical experimental evidence strongly indicate that the cytokine milieu in the tumor microenvironment plays a decisive role at all stages of CRC development as well as during cytotoxic therapy. Cytokines and other signal proteins control the plasticity of stromal, tumor and cancer stem like cells in an autocrine and paracrine manner thereby shaping the complex cellular contexture, which ultimately forms a pro- or anti-tumorigenic milieu. Thus, this Research Unit aims to gather a comprehensive functional understanding of mediator-dependent cellular and molecular events that are responsible for the plasticity of both stromal and tumor/stem cells.

The consortium will create a unique network bringing together leading basic and clinical scientists with complementary expertise in the fields of gastroenterology, immunology, pathology, surgery, molecular biology, cell biology and tumor biology that have one common goal: the development and preclinical assessment of novel strategies for prevention and therapy of CRC based on interference with cell plasticity in the tumor micro-environment. This powerful interdisciplinary network of clinical and basic scientists with a translational research focus that unify their expertise on a common topic will set the basis for the development of innovative therapeutic approaches that will go clearly beyond the current standard of care.

Collaboration between all FOR 2438 members
Z Project

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Project 8
Dr. Clemens Neufert & Prof. Dr. Marcus Neurath
The role of the IL-6/STAT3 axis in tumor fibroblasts during colorectal carcinogenesis

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Project 7
PD Dr. Andreas Weigert & Prof. Dr. Bernhard Brüne
Tumorigenic cytokine networks during colon carcinogenesis depend on sphingosine-1-phosphate receptor signalling

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Project 6
Dr. Rebecca Kesselring & Prof. Dr. Stefan Fichtner-Feigl
The cell-specific role of Interferon regulatory factor-5 for tumor cell plasticity and tumor progression during ulcerative colitis-associated and spontaneous colon tumorigenesis

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Project 5
Prof. Dr. Christoph Becker & Dr. Eva Martini
Functional role of Smad7 on intestinal epithelial homeostasis and colorectal cancer development

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Project 4
Dr. Henner Farin & Prof. Dr. Thomas Brabletz
The role of the EMT-inducer Zeb1 in the invasive tumor stroma during colon cancer progression

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Project 3
Prof. Dr. Florian Greten
Functional analysis of pathways mediating intestinal stem cell plasticity

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Project 2
PD Dr. Elisabeth Naschberger & Prof. Dr. Michael Stürzl
Endothelial cell-derived SPARCL1 as a regulator of tumor cell dormancy in colorectal cancer

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Project 1
Prof. Dr. Maximilian Waldner
The functional role of VEFGR2-signaling in CD4+ T cells in the pathogenesis of colorectal cancer

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