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09. Searching for the Cause of Spreading

Jun-Lin GuanJun-Lin Guan, Molecular Medicine, identified a specific metabolic pathway that allows cancer to spread, which could lead to drugs that will disrupt the process of metastasis. Guan and his graduate student pinpointed how connective tissue holding a cancer cell in place might degrade, disconnecting the diseased cell and allowing it to spread to other parts of the body. Using a cultured cell line from mice to create a model for studying cancer cells, the researchers discovered critical differences in how cancer cells and normal cells let materials enter through the membrane. Transforming a normal cell into one with features of cancer cells with a protein, v-Src derived from an oncogenic virus, the protein attached to an enzyme inside the cell. This set off events that blocked the entry through the cell’s membrane of some cell-surface proteins. One protein not allowed entry was MT1-MMP, which accumulated on the cell surface and also activated an enzyme, MMP2; acting together the two substances degraded the connective tissue that holds the cancerous cell in place. These cells float away, spreading around the body. Although v-Src has not been found in human cancer, other viruses—such as herpes and its relationship to cervical cancer—have been linked to cancer. The work offers insight into how cancer might spread. The work could stimulate related research with clinical impacts.

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