Regulation of the ErbB network by the MIG6 feedback loop in physiology, tumor suppression and responses to oncogene-targeted therapeutics. (February 2016)

• Record Type: Journal Article
• Authors: Anastasi, Sergio; Lamberti, Dante; Alemà, Stefano; Segatto, Oreste
• Is Part Of: Seminars in cell & developmental biology. Volume 50(2016)
• Page Start: 115
• Page End: 124
• Publication Date: 2016-02
• Subjects: RTK receptor tyrosine kinase -- EGF epidermal growh factor -- EGFR epidermal growth factor receptor -- LRIG1 leucin-rich repeats and immunoglobulin-like domains1 -- MIG 6mitogen inducible gene 6 -- RALT receptor associated late transducer -- ERRFI1 ErbB receptor feedback inhibitor 1 -- SOCS suppressor of cytokine signaling -- EBR ErbB binding region -- TKD tyrosine kinase domain -- ARF ADP-ribosylation factor -- RED RALT endocytic domain -- CBL casitas B-lineage lymphoma -- HGF hepatocyte growth factor -- PDGF platelet-derived growth factor -- FGF fibroblast growth factor -- GPCR G-protein coupled receptor -- JNK c-Jun N-terminal kinase -- MAPK mitogen-activated protein kinase -- ERK extracellular signal-regulated kinase -- FOS FBJ osteosarcoma oncogene -- AP-1 activator protein 1 -- LPA lysophosphatidic acid -- FOXO forkhead box, subgroup O -- EMT epithelial-mesenchimal transition -- UTR untranslated region -- HSP heat shock protein -- TKI tyrosine kinase inhibitor -- NSCLC non-small cell lung carcinoma -- IHC immuno-hystochemistry -- GBM glioblastoma multiforme -- TGFβ transforming growth factor beta -- PTEN phosphatase and tensin homolog -- SMAD similar to mothers against decapentaplegic -- CRC colorectal cancer -- DMBA dimethylbenzantracene -- DNMT DNA methyl-transferase -- PTC papillary thyroid carcinoma; MIG6 -- ErbB receptors -- Feedback inhibition -- Tumor suppression -- Targeted cancer therapeutics; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2015.10.001
• Languages: English
• ISSNs: 1084-9521

Abstract

Highlights: MIG6 plays a necessary role of in negative feedback regulation of ErbB receptors. MIG6 suppresses EGFR signaling via kinase inhibition and down-regulation. MIG6 loss enhances oncogenic ErbB signaling. MIG6 loss in tumors is a potential biomarker of oncogenic addiction to ErbB signaling. Abstract: The ErbB signaling network instructs the execution of key cellular programs, such as cell survival, proliferation and motility, through the generation of robust signals of defined strength and duration. In contrast, unabated ErbB signaling disrupts tissue homeostasis and leads to cell transformation. Cells oppose the threat inherent in excessive ErbB activity through several mechanisms of negative feedback regulation. Inducible feedback inhibitors (IFIs) are expressed in the context of transcriptional responses triggered by ErbB signaling, thus being uniquely suited to regulate ErbB activity during the execution of complex cellular programs. This review focuses on MIG6, an IFI that restrains ErbB signaling by mediating ErbB kinase suppression and receptor down-regulation. We will review key issues in MIG6 function, regulation and tumor suppressor activity. Subsequently, the role for MIG6 loss in the pathogenesis of tumors driven by ErbB oncogenes as well as in the generation of cellular addiction to ErbB signaling will be discussed. We will conclude by analyzing feedback inhibition by MIG6 in the context of therapies directed against ErbB and non-ErbB oncogenes.