SFB 850:  Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis

• Subject Area: Medicine ; Biology
• Term: from 2010 to 2021
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 89986987

Despite significant advances in cancer research and oncology metastasis remains the leading cause of cancer-related death. Many steps of the metastatic cascade are built on the aberrant reactivation of biological processes operative in embryogenesis, organogenesis and tissue regeneration. The CRC 850 studies changes in cell-cell adhesion and cell-matrix interactions as a prerequisite for cell motility in embryogenesis and cancer. Investigations on different modes of cellular motility have been in the focus of research. Initiation of cellular delamination and invasion as well as the mode of cellular migration are preset by cell intrinsic properties. In cancer cells altered (epi)genetic programs, e.g. triggered by oncogenic mutations, can induce reduction of cellular adhesion and increase cellular motility. These changes of cancer cell behavior are less stringently regulated by cell intrinsic oncogenic signaling as hitherto anticipated. Microenvironmental stimuli can modulate these oncogenic signals to revert the high mobility and invasiveness of cancer cells once they successfully colonized a foreign tissue. The dynamic switch of cancer cells between epithelial and mesenchymal states, i.e. epithelial-to-mesenchymal and mesenchymal-to-epithelial transition (EMT and MET), provides an opportunity for therapeutic intervention, as the transition from one state to the other alters the expression of putative drug targets and affects the proliferative and self-renewing capacity of cancer cells. The CRC 850 will analyze the different modes of cell motility in the context of cell plasticity and with respect to the influence of the microenvironment during developmental processes and cancer progression and invasion. To reflect the tremendous progress in the field, we decided to incorporate novel aspects into the already existing lines of research in our collaborative research center. One new focus of several projects is to link the epigenetic state of cancer cells and its dynamic regulation by microenvironmental factors to the adhesive and migratory properties of cancer cells. This approach has great potential for translation into the clinic, since epigenetic modifiers are in multiple cases druggable. Concerning cancer therapy, the tumor microenvironment is now recognized as a critical modulator for clinical responses to chemotherapy, kinase-inhibitor based targeted therapy and immunotherapy. Hence, these aspects have been strengthened by including projects investigating the movements of immune cells into cancers as well as inflammatory responses in murine cancer models. These projects will be strongly supported by novel imaging technologies in which the combination of intra-vital microscopy and the genetic labeling of immune cells and extracellular matrix components allow for the real-time analysis of the dynamic microenvironments.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Mechanisms controlling cell adhesion and motility in zebrafish stem cell proliferation zones (Project Head Driever, Wolfgang )
• A02 - Mechanisms underlying migration directionality in a collectively migrating cell group (Project Head Lecaudey, Virginie )
• A03 - Advanced imaging of dynamic ECM – cell interactions using genetically encoded live-reporters during cell migration in development and in adult tissues (Project Heads Arnold, Sebastian J. ;  Lämmermann, Ph.D., Tim )
• A04 - The role of the cadherin switch compared to Zeb1-dependent EMT in embryogenesis and tumor formation (Project Heads Brabletz, Thomas ;  Stemmler, Marc )
• A05 - Regulation of â-Catenin Function by NIP (Project Head Grosschedl, Rudolf )
• A06 - Non-cellautonomous role of the endoribonuclease ENDU-2/ENDOU/PP11 in tumorigenesis and invasion (Project Head Baumeister, Ralf )
• A07 - Control of cell migration in response to injury by the cancer-associated adhesion molecule EpCAM (Project Head Walz, Gerd )
• A08 - Control of epithelial cell extrusion (Project Head Classen, Anne-Kathrin )
• B02 - Role of the EMT activator ZEB1 in pancreatic cancer invasion, dissemination and metastasis (Project Heads Brabletz, Thomas ;  Brabletz, Simone )
• B03 - The novel arginine methyltransferase PRMT10 controls tumor growth and metastatic disease (Project Head Schüle, Roland )
• B04 - Understanding the role of the BRAFV600E oncoprotein in colorectal cancer initiation and metastasis (Project Head Brummer, Tilman )
• B05 - Control of tumor cell proliferation, migration and invasion by SNAIL1-induced changes in Wnt and BMP pathway activity (Project Head Hecht, Andreas )
• B06 - Transmembrane collagen XVII: role in cell migration and -invasion (Project Heads Bruckner-Tuderman, Leena Kaarina ;  Franzke, Ph.D., Claus-Werner )
• B07 - Therapeutic impact of protease deficiency on breast cancer invasion and metastasis (Project Heads Peters, Christoph ;  Reinheckel, Thomas )
• B08 - Integrating signaling networks of cell adhesion, cell motility, and tumor-stroma interactions (Project Heads Dengjel, Jörn ;  Schilling, Oliver )
• B09 - Epigenetic regulation of TGF-ß/BMP signaling and of EMT control of colon cancer invasion (Project Head Timmers, Marc )
• B10 - Epigenetic dysregulation in clear cell renal cell carcinoma metastasis (Project Head Frew, Ian )
• B11 - Cancer – microenvironment interactions in the progression to invasive squamous cell carcinoma (Project Head Nyström, Alexander )
• B13 - Mechanisms of tumorigenesis and metastasis formation by the phos-phatase PRL-3 (Project Head Köhn, Maja )
• C01 - Targeting Oncogenic Signaling Pathways with Interfering Peptides to Inhibit Tumor Growth and Metastasis (Project Head Arndt, Katja Maren )
• C02 - Minor splicing generates tumorigenic Rac variants in prostate cancer (Project Heads Aktories, Klaus ;  Schmidt, Gudula )
• C03 - The Chemokine Receptor CXCR4 in Small Cell Lung Cancer (SCLC) and its Role in Metastasis (Project Head Burger, Meike )
• C04 - Role of the Hedgehog Signaling Mediators Smo and STK36 (Fused) in Metastasis and Cancer Stem Cell Maintenance of Solid Tumors (Project Head Dierks, Christine )
• C05 - ErbB, Src and interactive signaling pathways in esophageal cancers (Project Head Laßmann, Silke )
• C06 - The role of miR-146a for cell migration in the tumor microenvironment (Project Head Zeiser, Robert )
• C08 - Role of the EMT and cellular motility in cancer stem cells isolated from triple negative breast cancer (Project Heads Maurer, Jochen ;  Stickeler, Elmar )
• C09 - Integrated Co-clinical Analysis of 3-D Tumor Organoids to Target Invasion and Metastasis in Pancreatic Cancer (Project Heads Börries, Melanie ;  Fritsch, Ralph )
• C10 - Control of T cell motility by the biophysical properties of the tumor stroma (Project Head Minguet, Ph.D., Susana )
• C11 - The role of local tumor barrier function for tumor cell plasticity, invasion and metastasis of colorectal cancer (Project Heads Fichtner-Feigl, Stefan ;  Kesselring, Rebecca )
• MGK - Integrated Research Training Group on Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis (Project Heads Börries, Melanie ;  Lecaudey, Virginie )
• Z01 - Systems biology, pathology and proteomics (Project Heads Busch, Hauke ;  Börries, Melanie ;  Laßmann, Silke ;  Schilling, Oliver )
• Z02 - In vivo animal imaging (Project Heads von Elverfeldt, Dominik ;  Meyer, Philipp Tobias ;  Reichardt, Wilfried ;  Zeiser, Robert )
• Z03 - Administration of the Collaborative Research Center (Project Head Peters, Christoph )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Participating Institution: Max-Planck-Institut für Immunbiologie und Epigenetik
• Spokesperson: Professor Dr. Christoph Peters