The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis - PubMed (original) (raw)

The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis

Angeles Duran et al. Cancer Cell. 2008 Apr.

Free article

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.

PubMed Disclaimer

Similar articles

• NF-kappa B is required for H-ras oncogene induced abnormal cell proliferation and tumorigenesis.
  Jo H, Zhang R, Zhang H, McKinsey TA, Shao J, Beauchamp RD, Ballard DW, Liang P. Jo H, et al. Oncogene. 2000 Feb 17;19(7):841-9. doi: 10.1038/sj.onc.1203392. Oncogene. 2000. PMID: 10702792
• 4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IkappaB kinase: potential role of reactive oxygen species.
  Park SA, Na HK, Kim EH, Cha YN, Surh YJ. Park SA, et al. Cancer Res. 2009 Mar 15;69(6):2416-24. doi: 10.1158/0008-5472.CAN-08-2177. Epub 2009 Mar 10. Cancer Res. 2009. PMID: 19276383
• TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation.
  Funakoshi-Tago M, Kamada N, Shimizu T, Hashiguchi Y, Tago K, Sonoda Y, Kasahara T. Funakoshi-Tago M, et al. Cytokine. 2009 Feb;45(2):72-9. doi: 10.1016/j.cyto.2008.10.010. Epub 2008 Dec 16. Cytokine. 2009. PMID: 19091594
• NF-kappaB signaling pathway and its therapeutic implications in human diseases.
  Sarkar FH, Li Y, Wang Z, Kong D. Sarkar FH, et al. Int Rev Immunol. 2008;27(5):293-319. doi: 10.1080/08830180802276179. Int Rev Immunol. 2008. PMID: 18853341 Review.
• p62 at the crossroads of autophagy, apoptosis, and cancer.
  Moscat J, Diaz-Meco MT. Moscat J, et al. Cell. 2009 Jun 12;137(6):1001-4. doi: 10.1016/j.cell.2009.05.023. Cell. 2009. PMID: 19524504 Free PMC article. Review.

Cited by

• NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis.
  Li W, Jin K, Luo J, Xu W, Wu Y, Zhou J, Wang Y, Xu R, Jiao L, Wang T, Yang G. Li W, et al. Front Cardiovasc Med. 2022 Sep 20;9:988266. doi: 10.3389/fcvm.2022.988266. eCollection 2022. Front Cardiovasc Med. 2022. PMID: 36204587 Free PMC article. Review.
• Autophagy as a Potential Therapy for Malignant Glioma.
  Escamilla-Ramírez A, Castillo-Rodríguez RA, Zavala-Vega S, Jimenez-Farfan D, Anaya-Rubio I, Briseño E, Palencia G, Guevara P, Cruz-Salgado A, Sotelo J, Trejo-Solís C. Escamilla-Ramírez A, et al. Pharmaceuticals (Basel). 2020 Jul 19;13(7):156. doi: 10.3390/ph13070156. Pharmaceuticals (Basel). 2020. PMID: 32707662 Free PMC article. Review.
• Clinical and Prognostic Value of PPIA, SQSTM1, and CCL20 in Hepatocellular Carcinoma Patients by Single-Cell Transcriptome Analysis.
  Mou L, Jia C, Wu Z, Xin B, Liang Zhen CA, Wang B, Ni Y, Pu Z. Mou L, et al. Cells. 2022 Sep 30;11(19):3078. doi: 10.3390/cells11193078. Cells. 2022. PMID: 36231045 Free PMC article.
• p62: a hub of multiple signaling pathways in HER2-induced mammary tumorigenesis.
  Cai-McRae X, Karantza V. Cai-McRae X, et al. Mol Cell Oncol. 2015 Mar 17;2(3):e975035. doi: 10.4161/23723556.2014.975035. eCollection 2015 Jul-Sep. Mol Cell Oncol. 2015. PMID: 27308451 Free PMC article.
• miR675 Accelerates Malignant Transformation of Mesenchymal Stem Cells by Blocking DNA Mismatch Repair.
  Lu Y, Song S, Jiang X, Meng Q, Wang C, Li X, Yang Y, Xin X, Zheng Q, Wang L, Pu H, Gui X, Li T, Lu D. Lu Y, et al. Mol Ther Nucleic Acids. 2019 Mar 1;14:171-183. doi: 10.1016/j.omtn.2018.11.010. Epub 2018 Nov 24. Mol Ther Nucleic Acids. 2019. PMID: 30594073 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • Mouse Genome Informatics (MGI)