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Gastro 2016
August 11-12, 2016
Volume 6, Issue 4(Suppl) J Gastrointest Dig Syst 2016
ISSN:2161-069X JGDS, an open access journal
conferenceseries .com
August 11-12, 2016 Birmingham, UK
6th Global Gastroenterologists Meeting
Ulrike Stein, J Gastrointest Dig Syst 2016, 6:4(Suppl)
Novel key players in cancer metastasis and signaling-based inventions for metastasis restriction
Ulrike Stein1,2
1Charité Universitätsmedizin Berlin, Germany
2Max-Delbrück-Center for Molecular Medicine, Germany
Metastatic dissemination of primary tumors is directly linked to patient survival in many tumor entities and critically
limits successful therapy. In human colorectal cancer (CRC), we identified the novel gene Metastasis Associated in Colon
Cancer 1, MACC1. MACC1 regulates fundamental processes like proliferation, motility, and dissemination in cell culture
and metastasis in mouse models. MACC1 regulates the transcription of genes able to induce metastasis by themselves; e.g.,
it was identified as a master regulator of c-Met. In CRC patient tumors and blood, MACC1 is a tumor stage-independent
predictor for metastasis and survival, allowing early identification of high-risk patients. MACC1 is confirmed as prognostic
and predictive biomarker and decisive driver for tumorigenesis and metastasis in a broad variety of solid cancers, correlating
to patient survival. MACC1 inhibitors are not available so far. Thus, we developed MACC1-signaling based interventions for
metastasis restriction. First, we identified the gene promoter of MACC1, unveiled its transcriptional regulation, and employed
theMACC1 promoter for high throughput screenings. We identified the first transcriptional small moleculeMACC1 inhibitors.
These drugs restrict MACC1-induced metastasis in mice. Furthermore, we addressed the impact of MACC1 post-translational
modifications for developing intervention strategies. Using mass spectrometry, we identified kinases phosphorylating MACC1.
Targeting the kinase for MACC1 tyrosine phosphorylation with inhibitors employed in clinical trials restricts MACC1-induced
tumor growth and metastasis in mice. In summary, transcriptional and post-translational regulations of MACC1 are druggable
by small molecules inhibitors. We present first MACC1-signaling based interventions for restriction of tumor progression and
metastasis of CRC.
Biography
Ulrike Stein has completed his PhD from the Humboldt University Berlin, Post-doctoral studies from the National Cancer Institute/NIH Frederick MD, her habilitation
from the Charité Universitätsmedizin Berlin and was 2009 appointed as Professor. She heads the research group of Translational Oncology of Solid Tumors at the
Experimental and Clinical Research Center, Charité and Max-Delbrück-Center for Molecular Medicine in Berlin. She has published more than 130 papers in reputed
journals, reveiced national and international scientific awards, is contributing to scientific consortia, is serving as Editorial Board Member of several journals, and
acts as reviewer for journals and funding organizations.