Researchers from University of Texas MD Anderson cancer center have indicated that altering tumor suppressor gene p53 family members may induce rapid regression of tumors lack of p53. This study was published in Nature.

TP53 is commonly altered in human cancer and the Tp53 reactivation suppresses tumors in vivo in mice (TP53 and Tp53 are also known as p53). This strategy has proven difficult to implement therapeutically.

In this study, scientists try to examine an alternative strategy by manipulating the p53 family members, Tp63 and Tp73 (also known as p63 and p73). The acidic transactivation-domain bearing (TA) isoforms of p63 and p73 structurally and functionally resemble p53, whereas the δN isoforms of p63 and p73 are frequently overexpressed in cancer and act primarily in a dominant-negative fashion against p53, TAp63 and TAp73 to inhibit their tumour-supressive functions. The researchers have shown that the deletion of δN isoforms of p63 or p73 leads to metabolic reprogramming and regression of p53-deficient tumours through upregualtion of IAPP, the gene that encodes amylin.

In addition, they found that IAPP is causally involved in this tumor regression and that amylin functions through the calcitonin receptor (CalcR) and receptor activity modifying protein 3 (RAMP3) to inhibit glycolysis and induce reactive oxygen species and apoptosis.

This study provides new insight of targeting tumors which are lack of p53 or with p53 mutation. Meanwhile, the researchers also identify the key receptors of cancer cells which are eliminated of p53 gene. These receptors may be potential prognostic markers to ensure if pramlintide will be effective to cure the patients with p53 mutation or lack of p53.

Reference:

Venkatanarayan A, Raulji P, Norton W, et al. IAPP-driven metabolic reprogramming induces regression of p53-deficient tumours in vivo[J]. Nature, 2014.