Non-canonical p53 signaling to promote invasion

It has been known for a number of years that mutated “inactive” p53 proteins still capable of binding to DNA per se, can bind to DNA sequences that are non-canonical for p53, with for example, a resultant increase in the transcription and expression of growth factor receptors such as ERBB1,(1)(,)(2) i.e., mutation of p53 not merely results in “no p53 function” but in fact results in “oncogenic p53 function”. And in agreement with this postulate transduction of p53 null cells with mutant p53 can cause transformation.(3) In prior studies the authors of the present manuscript had demonstrated that expression of p53 (R175H) and ERBB1 could transform immortalized primary esophageal cells, in parallel with increased migratory ability.(4) These present studies have defined why those transformed cells became invasive: increased c-Met activity.(5)