Study uncovers epigenetic driver of bone metastasis in advanced prostate cancer

MD Anderson Research Highlight May 20, 2025

Nearly 80% of men with advanced prostate cancer develop bone metastases, leading to bone pain, fractures and a poor prognosis. Using laboratory models, researchers led by Chenling Meng, Ph.D., Yue Lu, Ph.D., and Di Zhao, Ph.D., examined the epigenetic factors involved in prostate cancer metastasizing to the bone. They found that histone methyltransferase ASH1L is genetically amplified and overexpressed in several metastatic cancer types. Additionally, ASH1L interacts with the H1F-1α protein to rewire metastasis-associated genes in prostate cancer cells, making them more aggressive and more likely to spread to the bone. There, prostate cancer cells can influence nearby immune cells, turning them into lipid-associated macrophages that facilitate a pro-tumor environment. Inhibiting this ASH1L and H1F-1α pathway reduced bone metastasis in preclinical models, highlighting ASH1L as an epigenetic driver of bone metastasis and an actionable therapeutic target for metastatic prostate cancer. Learn more in Nature Communications.