Researchers at the University of Michigan Health Rogel Cancer Center have uncovered a key reason why a typically normal protein goes awry and fuels cancer. They found the protein NSD2 alters the function of the androgen receptor, an important regulator of normal prostate development. When androgen receptor binds with NSD2, it causes rapid cell division and growth leading to prostate cancer.
The study, published in Nature Genetics , may suggest a new way to therapeutically target prostate cancer. The findings illuminate a phenomenon not previously understood. The androgen receptor's normal function is to define the development of the prostate.
It tells the cells to stop growing and maintain a normal prostate. But in cancer, androgen receptor does the opposite: it tells the cells to continue growing and drive cancer development. Our study is one of the first molecular explanations for this functional duality of the androgen receptor.
NSD2 is a cancer specific collaborator of the androgen receptor that essentially rewires its activity to support prostate cancer development." Abhijit Parolia, Ph.D.
, study first author, Rogel fellow and assistant professor of pathology at Michigan Medicine Researchers started with a CRISPR screening to look for cofactors involved in the androgen receptor and prostate cancer. They scoured the enhanceosome, a complex of multiple proteins, including transcription factors and other epigenetic factors, that assemble on the DNA at specific sites to driv.