ΔNp63α regulates Erk signaling via MKP3 to inhibit cancer metastasis.

ABSTRACT: Reduced expression of the p53 family member p63 has been suggested to play a causative role in cancer metastasis. Here, we show that ΔNp63α, the predominant p63 isoform, plays a major role in regulation of cell migration, invasion and cancer metastasis. We identified mitogen-activated protein (MAP) kinase phosphatase 3 (MKP3) as a downstream target of ΔNp63α that is required for mediating these effects. We show that ΔNp63α regulates extracellular signal-regulated protein kinases 1 and 2 (Erk1/2) activity via MKP3 in both cancer and non-transformed cells. We further show that exogenous ΔNp63α inhibits cell invasion and is dependent on MKP3 upregulation for repression. Conversely, endogenous pan-p63 ablation results in increased cell migration and invasion, which can be reverted by reintrodu

SUBMITTER: Bergholz J 

PROVIDER: S-EPMC3962654 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature