A07
Reprogramming of the E3 ligase/DUB network during oncogenic transformation
Project Summary
Targeting essential pathways and exploiting tumor-intrinsic vulnerabilities holds the potential to improve current treatment for both early- and late-stage tumor patients. One central mechanism which is altered during oncogenic transformation within tumor cells is the ubiquitin proteasome system. Compared to non-transformed cells, cancer cells develop dependencies on individual components of the ubiquitin system, e.g. tumor-intrinsic mutations establish specific addictions towards the expression of distinct members of the UPS. In this project, we are investigating the combinatorial interplay of E3 ligase(s) and deubiquitinases (DUBs) during oncogenic reprograming in lung cancer. In particular, we will address the following aims: (i) Determine to which extent specific DUBs aid in establishing the ‘hallmarks of cancer’ in cells undergoing oncogenic reprogramming in NSCLC and (ii) explore the context-dependent switch of tumour-suppressive E3-ligases to an oncogenic role and (iii) small molecule and degrader mediated targeting of the proto-oncogenic DUBs and E3 ligases.
