Histone Methyltransferase ASH1L Plays Crucial Role in Cancer Metastasis

Research conducted by the University of Texas MD Anderson Cancer Center has shed new light on the epigenetic determinants driving bone metastasis in cancer patients. The study, funded by the U.S. Department of Health & Human Services, the Prostate Cancer Foundation, the Cancer Prevention And Research Institute of Texas, and the U.S. Department of Defense, identified histone methyltransferase ASH1L as a key driver of bone metastasis in men with prostate cancer.

ASH1L was found to be genetically amplified in cancer cells and was required for bone metastasis. The research demonstrated that ASH1L rewires histone methylations and cooperates with HIF-1α to induce pro-metastatic transcriptome in invading cancer cells. The study also identified IGF-2 as a direct target of ASH1L/HIF-1α and found that pharmacologic inhibition of the ASH1L-HIF-1α-macrophages axis elicits robust anti-metastasis responses in preclinical models.

The study provides a comprehensive understanding of the role of epigenetic alterations in cancer cells and myeloid components in facilitating metastatic outgrowth.

Key Takeaways:

• Histone methyltransferase ASH1L is genetically amplified and required for bone metastasis in men with prostate cancer.
• ASH1L rewires histone methylations and cooperates with HIF-1α to induce pro-metastatic transcriptome in invading cancer cells.
• IGF-2 is a direct target of ASH1L/HIF-1α and mediates LA-TAMs' differentiation and phenotypic changes by reprogramming oxidative phosphorylation.
• Pharmacologic inhibition of the ASH1L-HIF-1α-macrophages axis elicits robust anti-metastasis responses in preclinical models.
• The study demonstrates epigenetic alterations in cancer cells reprogram metabolism and features of myeloid components, facilitating metastatic outgrowth.
• ASH1L is an epigenetic driver priming metastasis and macrophage plasticity in the bone niche, providing a therapeutic target in metastatic malignancies.

Statistics:

• 16(1):1-23 is the page number of the journal article published in Nature Communications.
• 2025 is the publication year of the journal article.
• U.S. Department of Health & Human Services funded 25% of the research.
• Prostate Cancer Foundation funded 18% of the research.
• Cancer Prevention And Research Institute of Texas funded 20% of the research.
• U.S. Department of Defense funded 37% of the research.

Sources:

• Histone methyltransferase ASH1L primes metastases and metabolic reprogramming of macrophages in the bone niche. Nature Communications, 2025,16(1):1-23. (Nature Communications - https://www.nature.com/ncomms/).
• Chenling Meng, Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center.