Only a Subset of Met-Activated Pathways Are Required to Sustain Oncogene Addiction

Bertotti, Andrea; Burbridge, Mike F.; Gastaldi, Stefania; Galimi, Francesco; Torti, Davide; Medico, Enzo; Giordano, Silvia; Corso, Simona; Rolland-Valognes, Gaëlle; Lockhart, Brian P.; Hickman, John A.; Comoglio, Paolo M.; Trusolino, Livio

doi:10.1126/scisignal.2000643

Cited by 89 publications

(100 citation statements)

References 56 publications

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“…2d). These data are in agreement with the known anti-apoptotic effects of HGF/SF (16,17) and with protection of MET-dependent caspase cleavages by HGF/SF (30,32). These results demonstrated that the GAB1 adaptor is cleaved by caspases under stress induction, leading to the generation of a unique and stable 35-kDa GAB1 fragment containing its central region.…”

Section: The Down-expression Of Gab1 In Stress Conditions Is Associatsupporting

confidence: 90%

Anti-apoptotic Role of Caspase-cleaved GAB1 Adaptor Protein in Hepatocyte Growth Factor/Scatter Factor-MET Receptor Protein Signaling

Goff

Leclercq

et al. 2012

Journal of Biological Chemistry

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Background: Although the GAB1 adaptor is the main partner of the MET receptor, its role under apoptotic stress is controversial. Results: During apoptosis, GAB1 is caspase-cleaved, generating a p35-GAB1 fragment that plays a pro-survival role in HGF/ SF-MET signaling by retaining some signal transduction properties of GAB1. Conclusion:The caspase-cleaved GAB1 can maintain HGF/SF-MET survival signaling. Significance: A caspase-generated protein fragment can be anti-apoptotic.

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Section: The Down-expression Of Gab1 In Stress Conditions Is Associatsupporting

confidence: 90%

Anti-apoptotic Role of Caspase-cleaved GAB1 Adaptor Protein in Hepatocyte Growth Factor/Scatter Factor-MET Receptor Protein Signaling

Goff

Leclercq

et al. 2012

Journal of Biological Chemistry

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“…Modulation of the EGFR signaling pathway. A, the EGFR pathway interaction map is adapted from Bertotti and colleagues (41) and indicates the phospho-proteins measured by Bio-Plex analysis in pink, and proteins determined by immunohistochemistry on the tissue microarray or by Western blot in yellow. B, the heatmap clusters the samples and phospho-proteins by similarity.…”

Section: Discussionmentioning

confidence: 99%

Pathway Analysis of Glioblastoma Tissue after Preoperative Treatment with the EGFR Tyrosine Kinase Inhibitor Gefitinib—A Phase II Trial

Hegi

Diserens

Bady

et al. 2011

Molecular Cancer Therapeutics

173

109

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Amplification of the epidermal growth factor receptor (EGFR) gene is one of the most common oncogenic alterations in glioblastoma (45%) making it a prime target for therapy. However, small molecule inhibitors of the EGFR tyrosine kinase showed disappointing efficacy in clinical trials for glioblastoma. Here we aimed at investigating the molecular effects of the tyrosine kinase inhibitor gefitinib on the EGFR signaling pathway in human glioblastoma. Twenty-two patients selected for reoperation of recurrent glioblastoma were treated within a phase II trial for 5 days with 500 mg gefitinib before surgery followed by postoperative gefitinib until recurrence. Resected glioblastoma tissues exhibited high concentrations of gefitinib (median, 4

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“…Although MET signaling is primarily mediated by the Ras-MAPK and PI3K-AKT pathways (Bertotti et al 2009), other downstream effectors such as NF-kB, b-catenin, and STAT3 have been linked to MET. NF-kB contributes to HGF/SF-mediated proliferation and tubulogenesis through ERK1/2 and p38 MAPK (Muller et al 2002).…”

Section: Gab1 Gab1 H G F / S F H G F / S F Hgf/sfmentioning

confidence: 99%

MET: A Critical Player in Tumorigenesis and Therapeutic Target

Graveel

Tolbert

Woude

2013

Cold Spring Harbor Perspectives in Biology

112

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Since its discovery more than 25 years ago, numerous studies have established that the MET receptor is unique among tyrosine kinases. Signaling through MET is necessary for normal development and for the progression of a wide range of human cancers. MET activation has been shown to drive numerous signaling pathways; however, it is not clear how MET signaling mediates diverse cellular responses such as motility, invasion, growth, and angiogenesis. Great strides have been made in understanding the pleotropic aspects of MET signaling using three-dimensional molecular structures, cell culture systems, human tumors, and animal models. These combined approaches have driven the development of MET-targeted therapeutics that have shown promising results in the clinic. Here we examine the unique features of MET and hepatocyte growth factor/scatter factor (HGF/SF) structure and signaling, mutational activation, genetic mouse models of MET and HGF/SF, and MET-targeted therapeutics.

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Only a Subset of Met-Activated Pathways Are Required to Sustain Oncogene Addiction

Abstract: Cells addicted to different oncogenic receptor tyrosine kinases develop common downstream mechanisms to sustain malignancy.

Cited by 89 publications

References 56 publications

Anti-apoptotic Role of Caspase-cleaved GAB1 Adaptor Protein in Hepatocyte Growth Factor/Scatter Factor-MET Receptor Protein Signaling

Anti-apoptotic Role of Caspase-cleaved GAB1 Adaptor Protein in Hepatocyte Growth Factor/Scatter Factor-MET Receptor Protein Signaling

Pathway Analysis of Glioblastoma Tissue after Preoperative Treatment with the EGFR Tyrosine Kinase Inhibitor Gefitinib—A Phase II Trial

MET: A Critical Player in Tumorigenesis and Therapeutic Target

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