Empowering an Alternative Tumor Suppressor Prevents p53-Dependent Cancers

In over half of human cancers, one of these genes, the gene that encodes the p53 tumor suppressor protein, is missing. The lack of this particular gene allows the development of tumors that grow aggressively and often cannot be treated.

Investigators at the Cold Spring Harbor Laboratory (NY, USA) have been seeking other cell proteins that could assume a tumor-suppressing role in the absence of p53. One promising candidate is a member of the p63 group of proteins known as Tap63, a protein that is usually present in most cancerous cells. When p53 is present, Tap63 tumor suppressing activity is not required to prevent tumor growth. However, when p53 is missing, Tap63 becomes important.

Findings published in the November 8, 2009 edition of the journal Nature Cell Biology revealed that amplification of TAp63 activity induced cell senescence, while loss of p63 enhanced sarcoma development in mice lacking p53. In a novel mouse model where Tap63 activity could be turned on or off while other p63 proteins were not affected, it was found that lack of both Tap63 and p53 resulted in the development of large and aggressive tumors. Active Tap63 prevented tumor formation whether p53 was present or not.

"We were very excited to see that TAp63 shuts down cancer completely independently of p53," said senior author Dr. Alea Mills, an assistant professor at Cold Spring Harbor Laboratory. "This means that we now have a way of attacking cancers that have damaged p53, which are very difficult to treat in the clinic. Robustly activating TAp63 might be a viable anticancer strategy in the future. Alternatively, finding ways to stabilize the TAp63 that is already being made in cells or blocking pathways that combat TAp63 activities might also work."

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Cold Spring Harbor Laboratory