Activation of NF-κB Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis
Year: 2002
Type: article
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.
Source: Molecular and Cellular Biology
Authors: Markus Müller, Alessandro Morotti, Carola Ponzetto
Institution: University of Turin
Language: English
Topic: NF-κB Signaling Pathways
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2136690190