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.
| Original language | English |
|---|---|
| Pages (from-to) | 115-124 |
| Number of pages | 10 |
| Journal | Seminars in Cell and Developmental Biology |
| Volume | 50 |
| DOIs | |
| Publication status | Published - Feb 1 2016 |
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Keywords
- ErbB receptors
- Feedback inhibition
- MIG6
- Targeted cancer therapeutics
- Tumor suppression
ASJC Scopus subject areas
- Developmental Biology
- Cell Biology
Cite this
Regulation of the ErbB network by the MIG6 feedback loop in physiology, tumor suppression and responses to oncogene-targeted therapeutics. / Anastasi, Sergio; Lamberti, Dante; Alemà, Stefano; Segatto, Oreste.
In: Seminars in Cell and Developmental Biology, Vol. 50, 01.02.2016, p. 115-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of the ErbB network by the MIG6 feedback loop in physiology, tumor suppression and responses to oncogene-targeted therapeutics
AU - Anastasi, Sergio
AU - Lamberti, Dante
AU - Alemà, Stefano
AU - Segatto, Oreste
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - ErbB receptors
KW - Feedback inhibition
KW - MIG6
KW - Targeted cancer therapeutics
KW - Tumor suppression
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UR - http://www.scopus.com/inward/citedby.url?scp=84959319850&partnerID=8YFLogxK
U2 - 10.1016/j.semcdb.2015.10.001
DO - 10.1016/j.semcdb.2015.10.001
M3 - Article
AN - SCOPUS:84959319850
VL - 50
SP - 115
EP - 124
JO - Seminars in Cell and Developmental Biology
JF - Seminars in Cell and Developmental Biology
SN - 1084-9521
ER -