Oncogenic regulation of C/EBPß in triple-negative breast cancer and its role in immune evasion
Our lab has shown that expression of the transcription factor isoform C/EBPß-LIP that is controlled by the nutrient and growth factor responsive mTORC1 pathway acts oncogenic when aberrantly expressed. Such aberrantly high LIP expression is found in human aggressive triple-negative breast cancer (TNBC) and we have shown that inhibition of LIP strongly reduces cell migration and invasion and induces cancer metabolism. Our transcriptome analysis indicates that LIP also suppresses genes important for recognition and clearing of cancer cells by the immune system. Thus, LIP may contribute to cancer immune evasion. Restoring the immune response against TNBC and in cancer general is a major therapeutic strategy and may be achieved through targeting of LIP expression. In addition, we discovered that the high expression of LIP found in TNBC cells are completely independent of mTORC1 signalling. This is in sharp contrast to cancer cells or any other cell type studied that all show canonical regulation of LIP by mTORC1. Therefore, in TNBC cells a specific oncogenic mechanism must exist that induces high LIP expression. Drugs targeting LIP expression or components of the involved regulatory pathway in TNBC may provide new and necessary options for better treatment.

You will be working in the Gene Regulation in Aging and Age-related Diseases research group of prof. dr. Cor Calkhoven as part of a project funded by the Dutch Cancer Society (KWF).

- MSc life science, medical biology or related areas and are aiming to perform research in the cancer field.
- Experience with molecular biology and cell culture techniques.
- Independence in thinking and working yet in interaction with other researches.
- Proficient in written and spoken English.

- Mentoring, supervision and training.
- Access to state-of-the art infrastructure.
- A stimulating international research environment.

It concerns a full-time appointment (36 h/week) for a period of four years to be concluded with a PhD examination. After one year, the performance of the candidate will be evaluated to decide whether there is sufficient progress to expect a successful completion of the PhD thesis within the coming three years.
Duration of the contract: one year with possibility for extension (funding available for four years).

Your salary will be a minimum of € 2.570,- gross per month in the first year and a maximum of € 3.271,- gross per month (scale PhD) in the final (4th) year, based on a full-time appointment. In addition, the UMCG will offer you 8% holiday pay, and 8.3% end-of-year bonus. The conditions of employment comply with the Collective Labour Agreement for Medical Centres (CAO-UMC).

More information
For more information see European Research Institute for the Biology of Ageing

ERIBA

The European Research Institute for the Biology of Aging (ERIBA) is a research institute at the University Medical Centre Groningen (UMCG). ERIBA aims to discover molecular mechanisms of ageing that can be used as targets to prevent or delay age-related diseases. Our research teams are working with different model systems and technology platforms and share their knowledge and expertise to accelerate discoveries. ERIBA is part of the central UMCG campus, located in a vibrant student town in the northern Netherlands. PhD students are enrolled in the Graduate School of Medical Sciences of the University of Groningen.