Cited by 543NF-κB Signaling PathwaysProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

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The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis

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Duran, Angeles, Linares, Juan F., Galvez, Anita S., Wikenheiser, Kathryn, Flores, Juana M., Diaz-Meco, Maria T., Moscat, Jorge·2008·Cancer Cell

DOI 10.1016/j.ccr.2008.02.001

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Abstract

The balance between cell death and survival, two critical aspects of oncogenic transformation, determines the outcome of tumorigenesis. Nuclear factor-kappaB (NF-kappaB) is a critical regulator of survival; it is induced by the oncogene Ras and, when inhibited, accounts for the cell death response of Ras-transformed cells. Here, we show that the signaling adaptor p62 is induced by Ras, its levels are increased in human tumors, and it is required for Ras-induced survival and transformation. p62-/- mice are resistant to Ras-induced lung adenocarcinomas. p62 is necessary for Ras to trigger IkappaB kinase (IKK) through the polyubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), and its deficiency produces increased reactive oxygen species (ROS) levels, which account for the enhanced cell death and reduced tumorigenicity of Ras in the absence of p62.

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Authors: Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T., & Moscat, J.
Affiliations: University of Cincinnati (US)
Universidad Complutense de Madrid (ES)
Corresponding author: Moscat, Jorge
ORCID: Flores, Juana M.
Moscat, Jorge
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2008-04
Volume: 13
Issue: 4
Pages: 343-354
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2008.02.001
OpenAlex: W1981912182
Cited by: 541
References: 51
Citations by year: 2026: 10 · 2025: 13 · 2024: 13 · 2023: 18 · 2022: 30 · 2021: 35 · 2020: 41 · 2019: 39 · 2018: 41 · 2017: 51 · 2016: 41 · 2015: 38 · 2014: 41 · 2013: 45 · 2012: 29
FWCI: 6.37
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1933 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Memorial Sloan-Kettering Cancer Center
Cincinnati Children's Hospital Medical Center
University of Cincinnati
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: p62, NF-κB signaling, oncogenic Ras, carcinogenesis, cell survival, cell death, TRAF6, IκB kinase, polyubiquitination, reactive oxygen species, lung adenocarcinoma, oncogenic transformation
MeSH terms: Animals, Cell Survival, Cell Transformation, Neoplastic, DNA-Binding Proteins, Humans, Lung Neoplasms, Neoplasms, Transcription, Genetic, Signal Transduction, NF-kappa B, RNA-Binding Proteins, Reactive Oxygen Species, ras Proteins, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice

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The Signaling Adaptor p62 Is an Important NF-κB Mediator in Tumorigenesis

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