Metabolic 'reprogramming' by the p53 gene family leads to tumor regression

We examined an alternative approach by manipulating the p53 family members, p63 and p73," said Flores. Flores described two "warring" versions of p63 and p73 that are at odds when it comes to tumor suppression. One version, known as transactivation domain-bearing, is structurally and functionally similar to p53 in their ability to suppress tumors. The other version, which lacks this transactivation domain, actually prevents p53 from stopping tumor growth.  Transactivation domains are specific regions within a protein known as a transcription factor that effect further downstream cellular responses. "The p53 family interacts extensively in cellular processes that promote tumor suppression," said Flores. "Thus, a clear understanding of this interplay in cancer is needed to treat tumors with p53 alterations." Flores' team found that by deleting the p63 and p73 versions that lacked transactivation domains, they were able to metabolically reprogram cells so that the cancer progression was stopped and reversed in p53-deficient tumors. This was accomplished through increasing levels of IAPP, a gene important to the body's use of insulin. IAPP encodes amylin, chains of amino acids that are co-secreted with insulin. Flores sees IAPP as significant in trying new therapeutic approaches for treating p53-deficient tumors. "We found that IAPP is involved in tumor regression and that amylin, the protein encoded by the IAPP gene, stops a cell's ability to metabolize glucose, leading to ...
Source: M. D. Anderson Cancer Center - News Releases - Category: Cancer & Oncology Source Type: news