Signaling Pathway Defined in Common Head and Neck Cancer

February 8, 2006

Scientists have known for years that the p53 protein is frequently inactivated in squamous cell carcinoma cells of the head and neck.  Given this finding, many of the initial attempts to treat the molecules underpinning these cancers have targeted p53 in hopes of turning on the apoptotic, or cell suicide, signaling pathway that it oversees in normal cells - and which tumor cells tend to deactivate to ensure their survival.  The problem is that not all so-called “p53-negative tumors” respond to treatments that aim to restore the apoptotic signal.  This finding has led researchers to assume that glitches in other signaling pathways might help the tumor cells survive.  In the January issue of the journal Cancer Cell, NIDCR grantees and colleagues define one of these confounding pathways.  They found that a protein often overproduced in squamous cell carcinoma cells called ΔNp63 seems to repress the apoptosis-mediating p73 protein.  When the scientists reduced the levels of ΔNp63 in the tumor cells, they found that p73 triggered a specific program of apoptosis that was independent of p53.  With further validation, this new pathway will help scientists to define more accurately the underlying molecular features of squamous cell carcinoma biopsies and help doctors to better tailor treatment to these protein signatures.