GRK 2762 - Research Projects
Project L 3Impact of somatic Lamin mutations on radiation response in lung cancer
Principal Investigator
Prof. Dr. rer. nat. Alexander Schramm
Clinic for Internal Medicine (Tumor Research)
University Hospital Essen
Summary
Radiation responses of cancer cells are governed by pathways involved in antioxidant defense and DNA damage repair. In addition, cell survival after radiotherapy also crucially depends on maintaining integrity of organelles such as the nuclear envelope (NE). NE proteins of the Lamin family have structural and regulatory functions, which depend at least in part on upstream kinase signaling. Lamins also control release of DNA into the cytosol, which serves as a trigger for innate immune responses and DNA damage repair (DDR). Moreover, Lamin composition is important for cell fate decision and e.g. loss of LaminB1 has been implicated in aggressiveness of lung cancer. So far, little is known on the role of an altered Lamin network in modifying the responses to ionizing radiation. This project will use genetically modified NSCLC cells to systematically explore the role of Lamin mutations in the cross-talk between radiation-induced damage to the NE, the upstream regulatory kinase network, DDR signaling, and cell survival.
Selected Publications
HER2 mediates clinical resistance to the KRASG12C inhibitor sotorasib, which is overcome by co-targeting SHP2. Ho CSL, Tüns AI, Schildhaus HU, Wiesweg M, Grüner BM, Hegedus B, Schuler M, Schramm A, Oeck S. Eur J Cancer. 2021 Dec;159:16-23. doi: 10.1016/j.ejca.2021.10.003. Epub 2021 Oct 26. PMID: 34715459
NTRK1/TrkA Signaling in Neuroblastoma Cells Induces Nuclear Reorganization and Intra-Nuclear Aggregation of Lamin A/C. Funke L, Bracht T, Oeck S, Schork K, Stepath M, Dreesmann S, Eisenacher M, Sitek B, Schramm A. Cancers (Basel). 2021 Oct 21;13(21):5293. doi: 10.3390/cancers13215293. PMID: 34771457
NTRK1/TrkA Activation Overrides the G2/M-Checkpoint upon Irradiation. Hassiepen C, Soni A, Rudolf I, Boron V, Oeck S, Iliakis G, Schramm A. Cancers (Basel). 2021 Nov 30;13(23):6023. doi: 10.3390/cancers13236023. PMID: 34885133