ArticleCancer science2006
Activation of MEK/ERK and PI3K/Akt pathways by fibronectin requires integrin alphav-mediated ADAM activity in hepatocellular carcinoma: a novel functional target for gefitinib.
Article in Cancer science, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 67 citations in OpenAlex.
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- Aberrant Methylation and Immune Microenvironment Are Associated With Overexpressed Fibronectin 1: A Diagnostic and Prognostic Target in Head and Neck Squamous Cell Carcinoma.Frontiers in molecular biosciences · 2021Article
- Different roles of integrin-β1 and integrin-αv for type IV secretion of CagA versus cell elongation phenotype and cell lifting by Helicobacter pylori.PLoS pathogens · 2020Article
- Expansion of Transdifferentiated Human Hepatocytes in a Serum-Free Microcarrier Culture System.Digestive diseases and sciences · 2020Article
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- Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.Hormones & cancer · 2018Article
- Uncovering and deciphering the pro-invasive role of HACE1 in melanoma cells.Cell death and differentiation · 2018Article
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- Extracellular matrix-mediated cellular communication in the heart.Journal of molecular and cellular cardiology · 2016Review
- p70 S6-kinase mediates the cooperation between Akt1 and Mek1 pathways in fibroblast-mediated extracellular matrix remodeling.Biochimica et biophysica acta · 2015Article
- Mechanisms of Gefitinib-mediated reversal of tamoxifen resistance in MCF-7 breast cancer cells by inducing ERα re-expression.Scientific reports · 2015Article
- Interstitial Fluid Flow Increases Hepatocellular Carcinoma Cell Invasion through CXCR4/CXCL12 and MEK/ERK Signaling.PloS one · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have shown that the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) inhibits the development of intrahepatic metastases of hepatocellular carcinoma CBO140C12, and EGFR transactivation by tumor necrosis factor-alpha is a possible target of gefitinib. In the present study, we focused on the fibronectin (FN)-dependent signaling pathway to further elucidate the antimetastatic activity of gefitinib in CBO140C12 cells. We initially observed that FN induced activation of extracellular signal-regulated kinase (ERK), p38 and Akt, as well as cell proliferation and CBO140C12 cell invasion. These responses were mediated by EGFR tyrosine kinase, because gefitinib inhibited these effects of FN. FN-induced ERK, p38 and Akt activation was partly blocked by the Arg-Gly-Asp (RGD)-pseudo-peptide FC-336, anti-alphav integrin antibody RMV-7, the broad-spectrum matrix metalloprotease inhibitor GM6001 and the broad spectrum a disintegrin and metalloprotease (ADAM) inhibitor TAPI-1. But these inhibitors had no effect on EGF-induced signaling pathways, suggesting that integrins and ADAM may be upstream components of EGFR in these responses. These results suggest that FN-induced activation of ERK, p38, Akt, cell proliferation and invasion was mediated, at least in part, via integrins, ADAM and EGFR, and that this FN-induced signaling pathway might be involved in the antimetastatic activity of gefitinib.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.