Role of Polycomb complexes in breast cancer
Speaker: Lluis Morey, Ph.D. Sylvester Comprehensive Cancer Center. Cancer Epigenetics Program. Human Genetics Department, University of Miami Miller School of Medicine. Miami, USA
Organizers: IRB Barcelona
Date: Thursday 20 December 2018, 12.00h
Place: Aula Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Dr. Salvador Aznar Benitah
Polycomb-group (PcG) proteins play essential roles in regulating genes required for cell lineage specification and embryonic development. Alterations in the expression, and mutations of Polycomb genes have long been linked to the occurrence of different cancer types. PcG proteins from at least two distinct complexes, the Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). Traditionally, PcG complexes have been associated with maintenance of gene repression mainly via histone-modifying activities. However, during the last years, increasing evidence indicate the PcG complexes can also positively regulate gene transcription in multiple biological processes, cellular stages and in cancer. We recently showed we show that RNF2, encoding RING1B, and other PRC1 genes are overexpressed in breast cancer. While PRC1 still exerts its repressive function, it is also recruited to oncogenic active enhancers. Mechanistically, we found that PRC1 complexes functionally associate with ERα and its pioneer factor FOXA1 in ER+ breast cancer cells, and with BRD4 in triple-negative breast cancer cells (TNBC). RING1B regulates enhancer activity and gene transcription not only by promoting the expression of oncogenes but also by regulating chromatin accessibility. I will discuss our progress towards understanding the RING1B-mediated molecular mechanisms in breast cancer.
Oncology Programme Seminar