Cellular Signaling

Eileen Reinz, Daniela Berg, Cindy Körner, Silvia Vega Rubin de Celis, Mireia Berdiel, Simone Borgoni, Emre Sofyali, Chiara Giacomelli, Stephan Bernhardt, Janine Jung, Xiaoya Li, Khalid Abnaof

Alterations in cellular signaling are major drivers of tumor diseases, including breast cancer. We are out to understand the molecular events that are induced by oncogenic mutations as well as by (targeted) therapeutic drugs in the context of immediate responses as well as during resistance acquisition. Further, we explore mechanisms that are exploited by cancer cells and drive oncogenic signaling.

Receptor tryrosine kinase signaling via the EGF-receptor family of RTKs is a central signaling path also in breast cancer. Amplification of receptors (ERBB2) and mutations in signaling (like PIK3CA) are key events in different subtypes. We use targeted therapeutics (i.e., inhibitors and therapeutic antibodies) to better understand the wiring and rewiring in disease conditions (BMBF e:Med project HER2Low). Targeted proteomics using reverse phase protein arrays is combined with functional genomics approaches to decipher signaling and cellular responses [e.g., Peckys et al. 2017] as well as to identify markers for risk classification [Sonntag et al. 2014].

On EGFR-signaling we have a long-time collaboration with the groups of Yosef Yarden and Eytan Domany (Weizmann Institute of Science). There, we analyze, for example, metastasys phenotypes in the context of breast cancer models [Golan-Lavi et al. 2017, Sas-Chen et al. 2016, Kedmi et al. 2015, Cohen-Dvashi et al. 2015, Ben-Chetrit et al. 2015, Köstler et al. 2013].

A number of projects identified tumor-suppressive miRNAs that affect amongst others NF-kB signaling in breast cancer (e.g. miR-520/373 family, miR-31 and miR-30c-2-3p [Keklikoglou et al 2012, Koerner et al 2013, Shukla et al 2015]). Current research continues to unravel the complex network of miRNAs, signaling pathways and cellular phenotypes such as response to chemotherapy or metastatic dissemination. Research on this topic is mainly carried out in vitro and will be validated using in vivo xenograft mouse models.

Collaborations

Signaling: Yosef Yarden (Rehovot), Özgür Sahin (Ankara), Niels de Jonge (Saarbrücken), Pernette Verschure (Amsterdam), Luca Magnani (London), Max Hasmann (Penzberg)

Bioinformatics: Tim Beissbarth (Göttingen), Rainer König (Jena), Zita Soons (Maastricht), Antoine van Kampen, Perry Moerland (Amsterdam)

Mathematical modeling: Jens Timmer (Freiburg), Stefan Legewie (Mainz)

Clinics: Andreas Schneeweiss, Peter Sinn (Heidelberg), Martina Vetter, Eva Kantelhardt (Halle/Saale)

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