FOR 2438:  Cell Plasticity in Colorectal Carcinogenesis

• Subject Area: Medicine
• Term: from 2016 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 280163318

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.

• DFG Programme: Research Units

Projects

• Analysis and functional modulation of the cross-talk between pSTAT3high cancer-associated fibroblasts and tumor cells in colorectal cancer (Applicants Neufert, Ph.D., Clemens ;  Neurath, Markus F. )
• Central project (Applicants Farin, Henner ;  Wirtz, Stefan )
• Coordination Funds (Applicant Greten, Florian R. )
• Coordination Funds (Applicant Greten, Florian R. )
• Functional analysis of pathways mediating intestinal stem cell plasticity (Applicant Greten, Florian R. )
• Functional role of Smad7 on intestinal epithelial homeostasis and colorectal cancer development (Applicants Becker, Christoph ;  Liebing, Eva )
• S1P receptors shape immune cell plasticity in colorectal carcinoma (Applicants Brüne, Bernhard ;  Weigert, Andreas )
• The cell-specific role of Interferon regulatory factor-5 for tumor cell plasticity and tumor progression during ulcerative colitis-associated and spontaneous colon tumorigenesis (Applicants Fichtner-Feigl, Stefan ;  Kesselring, Rebecca )
• The CXCL13-CXCR5 pathway as a regulator of adaptive immunity in colorectal cancer (Applicant Waldner, Ph.D., Maximilian )
• The functional role of VEGFR2-signaling in CD4+ T cells in the pathogenesis of colorectal cancer (Applicant Waldner, Ph.D., Maximilian )
• The role of plasma cell activation and metabolism in colorectal carcinogenesis and metastasis (Applicants Fichtner-Feigl, Stefan ;  Kesselring, Rebecca )
• The role of the EMT-inducer Zeb1 in the invasive tumor stroma during colon cancer progression (Applicants Brabletz, Thomas ;  Farin, Henner )
• The role of the EMT-inducer Zeb1 in the invasive tumor stroma during colon cancer progression (Applicants Brabletz, Thomas ;  Farin, Henner )
• Tumor microenvironment-dependent angiocrine tumor suppression in colorectal cancer (Applicants Naschberger, Elisabeth ;  Stürzl, Michael )
• Tumorigenic cytokine networks during colon carcinogenesis depend on sphingosine-1-phosphate receptor signalling (Applicants Brüne, Bernhard ;  Weigert, Andreas )

• Spokesperson: Professor Dr. Florian R. Greten