Loss of p53 Enhances NF-κB-Dependent Lamellipodia Formation

Tumor suppressor p53 prevents tumorigenesis and tumor growth by suppressing the activation of several transcription factors, including nuclear factor‐κB (NF‐κB) and STAT3. On the other hand, p53 stimulates actin cytoskeleton remodeling and integrin‐related signaling cascades. Here, we examined the p53‐mediated link between regulation of the actin cytoskeleton and activation of NF‐κB and STAT3 in MCF‐7 cells and mouse embryonic fibroblasts (MEFs). In the absence of p53, STAT3 was constitutively activated. This activation was attenuated by depleting the expression of p65, a component of NF‐κB. Integrin β3 expression and lamellipodia formation were also downregulated by NF‐κB depletion. Inhibition of integrin αvβ3, Rac1 or Arp2/3, which diminished lamellipodia formation, suppressed STAT3 activation induced by p53 depletion. These results suggest that loss of p53 leads to STAT3 activation via NF‐κB‐dependent lamellipodia formation. Our study proposes a novel role for p53 in modulating the actin cytoskeleton through suppression of NF‐κB, which restricts STAT3 activation. J. Cell. Physiol. 229: 696–704, 2014. © 2013 Wiley Periodicals, Inc.