We newly discovered the gene MACC1 (metastasis associated in colon cancer 1) and identified the metastasis inducer S100A4 as a Wnt signaling target gene. Transcriptional targets or protein binding partners thereof were found as new diagnostic, prognostic and predictive key players for tumor progression and metastasis.Biomarker development is done in established and patient-derived 3D cultures, cell line-derived and patient-derived xenograft (PDX) and newly generated genetically engineered mouse (GEMM) models.
We exploit this knowledge for improved disease prognosis and treatment response prediction in tissue and blood of cancer patients. Novel therapeutic approaches are currently tested in clinical trials to treat patients with metastatic disease using small molecule inhibitors acting on these biomarkers.
MACC1 induces cell motility, proliferation, and scattering in cell culture and metastasis in mouse models. It acts as transcription factor regulating e.g. Met expression, and also interacts with proteins via e.g. its SH3 domain or proline-rich motif. By microarrays we identified the MACC1 transcriptome. By HTS using the MACC1 promoter we identified first transcriptional MACC1 inhibitors. By MS we identified the MACC1 interactome and phospho-interactome for novel interventions.