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).