Cellular Signaling

Zhivka Hristova, Nooraldeen Tarade, Lukas Beumers, Janina Müller, Birgitta Michels, Efstathios Vlachavas, Sara Burmester, Angelika Wörner, Sabine Karolus, Daniela Heiss, Corinna Becki, Cindy Körner

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.

Resistance to endocrine therapies poses a major clinical problem, as such resistance develops in a siginificant number of patients under or after therapy. We have established cell line models of resistance and employed these to better understand molecular processes that change during resistance development and to discern the functional and, potentially, clinical consequences [Borgoni et al. 2020]. These mechanisms appear to involve epigenetic alterations. Along these lines we are out to understand the molecular consequences [Soleimani et al. 2020] and the underlying causes. We currently characterize clonal characteristics of therapy resistance, and the contribution of epigenetic enzymes in the process of resistance acquisition

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], to identify markers for risk classification [Sonntag et al. 2014, Bernhardt et al. 2017, Bernhardt et al. 2019].

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 (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]) and of TGFbeta signaling in breast cancer [Breunig et al. 2018]. 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 in 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)

Autophagy: Silvia Vega Rubin de Celis (Essen)

Bioinformatics: Lars Feuerbach, Benedikt Brors (DKFZ), 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, Christoph Thomssen (Halle/Saale)

to top
powered by webEdition CMS