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

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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

DOI 10.1128/mcb.22.4.1060-1072.2002PMC PMC134627

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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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Authors: Müller, M., Morotti, A., & Ponzetto, C.
Affiliations: University of Turin (IT)
Corresponding author: Ponzetto, Carola
ORCID: Morotti, Alessandro
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 2002-02-01
Volume: 22
Issue: 4
Pages: 1060-1072
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.22.4.1060-1072.2002
PMC: PMC134627
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: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Activation of NF-κB Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis

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