Cited by 129NF-κB Signaling PathwaysLiver physiology and pathologySignaling Pathways in Disease

Activation of NF-κB Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis

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Müller, Markus, Morotti, Alessandro, Ponzetto, Carola·2002·Molecular and Cellular Biology

Abstract

Hepatocyte growth factor (HGF) and its receptor, Met, regulate a number of biological functions in epithelial and nonepithelial cells, such as survival, motility, proliferation, and tubular morphogenesis. The transcription factor NF-kappaB is activated in response to a wide variety of stimuli, including growth factors, and is involved in biological responses in part overlapping with those triggered by HGF. In this work we used the liver-derived MLP29 cell line to study the possible involvement of NF-kappaB in HGF/Met signaling. HGF stimulates NF-kappaB DNA binding and transcriptional activation via the canonical IkappaB phosphorylation-degradation cycle and via the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase cascades. Phosphatidylinositol 3-kinase is not involved in Met-mediated NF-kappaB activation. Blockage of NF-kappaB activation in MLP29 cells by forced expression of the NF-kappaB super-repressor IkappaB(alpha)2A does not interfere with HGF-induced scatter but inhibits proliferation and tubulogenesis. Surprisingly, in the same cells NF-kappaB appears to be dispensable for the antiapoptotic function of HGF.

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Crossref · 10.1128/mcb.22.4.1060-1072.2002

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Authors
Müller, M., Morotti, A., & Ponzetto, C.
Affiliations
University of Turin (IT)
Corresponding author
Ponzetto, Carola
Venue
Molecular and Cellular Biology
Published
2002-02-01
Volume
22
Issue
4
Pages
1060-1072
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2136690190
Cited by
129
References
89
Citations by year
2026: 4 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 6 · 2014: 7 · 2013: 8 · 2012: 9
FWCI
2.65
Type
journal article
Language
en
Open access
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Fondazione CRT
  • Compagnia di San Paolo
  • Centre National de la Recherche Scientifique
  • Associazione Italiana per la Ricerca sul Cancro
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
NF-κB activation, hepatocyte growth factor, c-Met, tubulogenesis, cell proliferation, ERK signaling, p38 MAPK signaling, phosphatidylinositol 3-kinase, IκBα super-repressor, cell scattering, antiapoptotic function, liver
MeSH terms
NF-KappaB Inhibitor alpha, Animals, Cell Division, Cell Line, Cell Movement, DNA, DNA-Binding Proteins, Gene Expression Regulation, Humans, Liver, Morphogenesis, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Transcription, Genetic, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Apoptosis, Hepatocyte Growth Factor, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins c-met, I-kappa B Proteins, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Mice

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