title: Loss of p53 enhances NF-κB-dependent lamellipodia formation.
abstract: 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.
authors.forename: Alvin Kunyao
authors.initials: AK
authors.lastname: Guo
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Hou
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hirata
authors.forename: Shota
authors.initials: S
authors.lastname: Yamauchi
authors.forename: Ai Kia
authors.initials: AK
authors.lastname: Yip
authors.forename: Keng-Hwee
authors.initials: KH
authors.lastname: Chiam
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sawada
authors.forename: Keiko
authors.initials: K
authors.lastname: Kawauchi
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects* / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D039661:Integrin beta3; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D016159:Tumor Suppressor Protein p53; D051550:I-kappa B Kinase