Scientists ID Gene Pathway Triggering Melanoma Spread

Finding could lead to therapeutic applications for tumor progression in other cancers

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MONDAY, Sept. 29, 2008 (HealthDay News) -- Researchers say they have identified how a particular gene helps human melanoma cells spread throughout the body.

This finding could eventually lead to the development of anti-metastatic drugs for melanoma and other cancers, said members of the Virginia Commonwealth University team responsible for the discovery.

Metastatic disease is a major hurdle in cancer therapy, because treatment becomes more difficult, and in many instances ineffective, when the cancer spreads to remote sites through the lymph system and blood vessels.

The team found that melanoma differentiation associated gene-9/syntenin, or mda-9/syntenin, interacts with c-Src, an important signaling protein involved with tumor cell growth and metastasis. The gene increases the expression of c-Src that triggers a signaling cascade resulting in increased cancer cell motility, invasion and metastasis.

The findings are published in this week's issue of the Proceedings of the National Academy of Sciences.

"Mda-9/syntenin may represent a potential new molecular target for melanoma therapy that could be used to develop therapeutic reagents for treating this cancer as well as other cancers originating in the breast and stomach," Paul B. Fisher, chair of the VCU Department of Human and Molecular Genetics, said in a university news release.

"By disrupting the interaction between mda-9/syntenin and c-Src, it may be possible to prevent metastasis by blocking those signaling changes necessary for this process," he added.

Previous studies have shown that mda-9/syntenin regulates cell motility and can alter certain pathways affecting metastatic ability. This discovery provides the first understanding of the mechanisms involved.

The team plans to investigate whether small molecule drugs exist or can be developed to prevent metastasis by attacking the interplay between mda-9/syntenin and c-Src. Further studies are underway to find how these interactions may affect metastasis of other types of human tumors.

More information

The National Cancer Institute has more about melanoma.

SOURCE: Virginia Commonwealth University, news release, Sept. 29, 2008


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