Mda-9/synenin activates c-Src, setting off a signaling cascades that leads to increased cell motility and attack, according to study in PNAS.

Researchers have discovered how melanoma differentiation associated gene-9/syntenin (mda-9/syntenin) interacts with an important signaling protein to promote metastasis in human melanoma cells. Previous studies showed that mda-9/syntenin regulates cell motility and can alter certain biochemical and signaling pathways leading to metastasis. The exact mechanism involved, however, was not understood until now.

Investigators found that mda-9/syntenin physically interacts with c-Src, a key signaling protein involved with tumor cell growth and metastasis, to mediate invasion, migration, anchorage-independent growth, and metastasis.

The team examined human cancer cells in the laboratory using a relevant human melanoma metastasis model and discovered how mda-9/syntenin was able to activate the expression of c-Src. The expression of c-Src then led to an increase in the formation of an active FAK/c-Src signaling complex. This interaction triggers a signaling cascade resulting in greater cancer cell motility, invasion, and metastasis, according to the scientists.

The group will further investigate whether small molecule drugs can be identified and developed to prevent metastasis by targeting this interaction between mda-9/syntenin and c-Src. Other studies are in progress to determine how well these interactions mediate metastasis in human tumors other than melanoma.

Researchers from Virginia Commonwealth University and INSERM conducted this study. It is published in this week’s online early edition of Proceedings of the National Academy of Sciences.

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