Prof. Dr. Heike Allgayer

1a) Next generation sequencing and transcriptome analysis of total RNA from tumor and normal tissue of a colorectal cancer patient (UCSC Genome Browser). 1b) Chicken chorioallantoic membrane (CAM) assay: Primary tumor in the upper CAM.

Metastasis and related translational research represent a key interest of the CCU Molecular Oncology of Solid Tumors.

The group has contributed, e.g., to the discovery of major regulatory mechanisms driving expression of the urokinase receptor (u-PAR), one of the most relevant metastasis-related genes, and provided first evidence for tumor specificity of particular u-PAR transcriptional regulators in resected gastrointestinal cancers, delineating novel prognostic high-risk groups and molecular staging models. Furthermore, the group demonstrated that the novel tumor suppressor Pdcd4 inhibits metastasis by regulating u-PAR, and that the loss of Pdcd4 is an independent prognostic marker. As a major mechanism downregulating Pdcd4, the group described microRNA-21 which post-transcriptionally downregulates Pdcd4 and stimulates three different steps of the metastastic cascade. Regarding translational research, we found that the EGFR-antagonist Cetuximab attenuates in vivo metastasis and u-PAR gene expression in non-small cell lung cancer (NSCLC), and that u-PAR, with E-cadherin, is a novel biomarker of Cetuximab sensitivity in NSCLC.
Taken together, the group has shown that it is possible to individualize solid tumor staging by mechanisms regulating metastasis, and to define novel high-risk groups and response markers with them. Future activities will extend to systematic projects on master pathways of metastasis, microRNAs in metastasis, and implications for targeted therapy.