The metastatic cancers of mice developed a chromosomal amplification--a region of the genome expressed in an unusually large number of copies--that corresponded to a much larger amplified region in the metastatic human melanomas, they found. Further study of that common region in mouse melanomas that independently developed their invasive ability revealed just one consistently elevated protein, called Nedd9.
To find out whether Nedd9 could play a role in skin cancer's spread, the researchers blocked the protein in both mouse and human metastatic melanoma cells. Cancer cells without active Nedd9 lost their ability to invade. Similarly, primary melanomas, when made to express too much Nedd9, became invasive, identifying Nedd9 as a "bona fide melanoma metastasis gene." Nedd9's role appears to result from its interaction with another enzyme known to be important for cell's ability to migrate and take root.
As further evidence, they also found that the Nedd9 gene was frequently expressed at higher levels in metastatic human melanomas compared to primary melanomas.
Drugs aimed at Nedd9 might therefore prevent the skin cancer's spread, Chin said. Measurement of Nedd9 levels in primary melanomas might also provide an indication of the cancer's likelihood of spreading, although "any prognostic significance would require rigorous investigation and validation in appropriately designed prospective clinical trials."
Taking a similar approach, Lowe's team identified two genes that can work together to encourage one form of liver cancer, called hepatocellular carcinoma.
Hepatocellular carcinoma is the fifth most frequent form of cancer worldwide but, owing to the lack of effective treatment options, represents the third leading cause of death, Lowe said. The only curative treatments involve surgery or transplantation as chemotherapies are ineffective, and no existing dr
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Source:Cell Press