Poster Presentation 16th Asian Conference on Transcription 2019

Analysis of Menin in breast cancers reveals its role in cancer epigenome regulation (1183)

Taewan Kim 1 , Eun-Jung Cho 1
  1. Sungkyunkwan university, Suwon, GYEONGGI-DO, South Korea

Menin, encoded by the Multiple Endocrine Neoplasia Type 1 (MEN1), functions as a scaffold protein interacting with a variety of transcription factors to control active or repressive expression of target genes involved in myriad cellular processes. While menin has been originally reported as a tumor suppressor in pancreatic tumors, it is also associated with tumorigenesis by interaction with MLL to promote tumors in the blood and other solid tissues, including luminal breast cancer, prostate cancer, and liver cancer. These studies place firmly menin as a therapeutic target for the development of small molecules that inhibit Menin-MLL interaction. More recently, DAXX (Death-domain associated protein) a chaperone for histone H3.3, was identified as an interaction partner, to which Menin competes with H3.3 for binding. Since DAXX is involved in H3.3 loading through PML and global heterochromatin formation, Menin has a potential to affect the DAXX-dependent H3.3 deposition into chromatin via PML. In this study, We found that targeting Menin impairs the growth of breast cancer cells of both luminal and triple negative breast cancer (TNBC) types. Furthermore, we found that cellular localization of DAXX was profoundly affected upon inhibition of menin. The nuclear colocalization of DAXX with PML. foci was significantly increased by menin inhibition, indicating the impact of menin on H3.3 cancer epigenome. We further discuss the implication of Menin-DAXX-H3.3 interaction required for the chromatin dynamics during breast cancer tumorigenesis.