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

点击翻译按钮获取中文摘要

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.