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Background: Metastasis is a dangerous stage of cancer in which cancer cells have spread to other tissues in the body creating metastatic tumors. The protein c-MYC is considered the master regulator because it stimulates the epithelial-mesenchymal transition (EMT) which converts tumor cells into metastatic cells that can travel to other tissues. Most cancers have hyperactive c-MYC.

Research: ZNF281 is a protein that is known to interact with c-MYC and scientists in Munich, using colorectal cancer as a model, asked whether or not ZNF281 plays a role in metastasis. They found that the ZNF281 gene interacts with a protein called SNAIL and SNAIL’s ability to promote metastasis is dependent on its binding to ZNF281’s promoter. ZNF281 also promotes the translation of other products that drive the EMT (therefore causing metastasis).

So how is ZNF281 regulated? And what does SNAIL have to do with its regulation? SNAIL promotes metastasis by stimulating the production of ZNF281, and it does so by 2 feed forward mechanisms:

1. it activates transcription of the mRNA encoding for ZNF281
2. it represses the expression of miRNA-34a which inhibits ZNF281 through RNA interference (interestingly, miRNA-34a transcription is induced by the p53 tumor suppressor)

With a mouse model, the scientists found that colon cancer cells that did not contain ZNF281 could not metastasize. Therefore, “inhibition of ZNF281 prevents metastasis” in mice.

Think About:

1. How can these findings be used in cancer treatments/therapies?
2. What additional research do these findings inspire?

For More Information:

3. Metastasis:
4. Original Nature Journal Article: