Researchers at Yale Cancer Center have discovered a gene that has a dramatic impact on the growth of melanoma. Their observations, titled ”DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR,” were published in the journal Cell Reports. The study sheds light on how melanoma develops and describes a new target to possibly treat this type of cancer.
Researchers identified a new role for one type of DNA methyltransferase, DNMT3B, in melanoma growth regulation. DNA methyltranferases are enzymes that can chemically modify DNA, and they play critical roles in regulating gene expression during development.
Aberrant DNA methylation of specific genes occurs in all human melanoma, but the functional consequences of methylation and the role of individual methyltransferases in its development are poorly understood. “Despite a clear role for DNMT3B in a wide variety of human cancers, the signaling pathways that drive cancer formation that are critically affected by DNMT3B are largely unknown,” the authors explain in their study.
High expression levels of DNA methyltransferases are common in melanoma, which can switch genes between off and on states, contributing toward tumor progression. Researchers discovered a specific signaling pathway that is dependent on DNMT3B methyltransferases. They found that reducing the level of DNMT3B methyltransferases could slow melanoma formation in mice models of the disease. Moreover, reduction of this particular methyltransferase influenced mTORC2, a protein complex that regulates cell growth, size, and survival.
“We have identified a new target for drug development as well as a new way of targeting an existing pathway. These findings identify DNMT3B as an attractive target for cancer therapy,” study author Dr. Marcus W. Bosenberg, an associate professor at Yale School of Medicine, said in a news release.
“The reversible nature of DNA methylation is an attractive target for therapy. FDA-approved demethylating agents are used for treatment of myelodysplastic syndrome and AML as well as in clinical trials for combination therapy of solid tumors. Our results, taken together with studies suggesting a specific role for DNMT3B in gene body methylation and the requirement of DNMT3B in re-methylation in cancer, suggest that DNMT3B plays important, non-redundant roles in carcinogenesis and merits development of direct and specific inhibitors,” the authors wrote.