Methylation signaling controls angiogenesis and cancer growth

A study led by researchers at Boston University School of Medicine (BUSM) demonstrates a new mechanism involving a signaling protein and its receptor that may block the formation of new blood vessels and cancer growth. The findings are published in the December issue of Science Signaling.

Angiogenesis creates new blood vessels in a process that can lead to the onset and progression of several diseases such as cancer and age-related macular degeneration.

Vascular endothelial growth factor (VEGF) is a signaling protein produced by damaged cells, which binds to one of its receptors VEGFR-2, located on the surface of blood vessel cells. Once VEGF is bound to its receptor, it is activated and sends a biochemical signal to the inside of the blood vessel cell to initiate angiogenesis. There are currently multiple Federal Drug Administration-approved medications that target this process. However these medications are limited by insufficient efficacy and the development of resistance.

The researchers demonstrated that a biochemical process called methylation, which can regulate gene expression, also affects VEGFR-2, and this can lead to angiogenesis. Using multiple methods, the researchers were able to interfere with the methylation process of VEGFR-2 and subsequently block angiogenesis and tumor growth.

"The study points to the methylation of VEGFR-2 as an exciting, yet unexplored drug target for cancer and ocular angiogenesis, ushering in a new paradigm in anti-angiogenesis therapy," said Nader Rahimi, PhD, associate professor of pathology, BUSM, who served as the study's senior investigator.

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Ed Hartsough, a graduate student and Rosana Meyer, a postdoctoral fellow at the department of pathology, BUSM, are the co-primary authors. Funding for this study was provided in part by the National Institutes of Health through grant award numbers R01EY017955, P41 RR010888/GM104603, S10 RR020946, HHSN268201000031C and DK080946 AQ12 and the Massachusetts Lions Foundation.

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Jenny Eriksen
jenny.eriksen@bmc.org
617-638-6841
Boston University Medical Center