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Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins.

作者信息

Wang Wenqi, Li Nan, Li Xu, Tran My Kim, Han Xin, Chen Junjie

机构信息

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Cell Rep. 2015 Oct 20;13(3):524-532. doi: 10.1016/j.celrep.2015.09.014. Epub 2015 Oct 8.

DOI:10.1016/j.celrep.2015.09.014
PMID:26456820
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4618173/
Abstract

As the key effector in the Hippo pathway, YAP was identified as an oncoprotein whose expression is elevated in various human cancers. However, the development of potentially therapeutic compounds targeting YAP has been slow and limited. Here, we find that tankyrase inhibitors suppress YAP activity. This effect is mediated by anigomotin (AMOT) family proteins. Tankyrases associate with AMOT family proteins and promote their degradation through E3 ligase RNF146. By antagonizing tankyrase activity, tankyrase inhibitors stabilize AMOT family proteins, thereby suppressing YAP oncogenic functions. Together, our studies not only demonstrate the tankyrase-RNF146-AMOT axis as an upstream pathway regulating YAP but also reveal a therapeutic opportunity in targeting YAP for cancer treatment.

摘要

相似文献

[1]
Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins.

Cell Rep. 2015-10-20

[2]
Tankyrase Inhibitor Sensitizes Lung Cancer Cells to Endothelial Growth Factor Receptor (EGFR) Inhibition via Stabilizing Angiomotins and Inhibiting YAP Signaling.

J Biol Chem. 2016-7-15

[3]
The RNF146 and tankyrase pathway maintains the junctional Crumbs complex through regulation of angiomotin.

J Cell Sci. 2016-9-15

[4]
Tankyrase inhibitors suppress hepatocellular carcinoma cell growth via modulating the Hippo cascade.

PLoS One. 2017-9-6

[5]
Angiomotin stabilization by tankyrase inhibitors antagonizes constitutive TEAD-dependent transcription and proliferation of human tumor cells with Hippo pathway core component mutations.

Oncotarget. 2016-5-17

[6]
Regulation of localization and function of the transcriptional co-activator YAP by angiomotin.

Elife. 2017-5-3

[7]
Hippo pathway-independent restriction of TAZ and YAP by angiomotin.

J Biol Chem. 2011-1-11

[8]
The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis.

Sci Signal. 2013-9-3

[9]
Amot130 adapts atrophin-1 interacting protein 4 to inhibit yes-associated protein signaling and cell growth.

J Biol Chem. 2013-4-5

[10]
Serum deprivation inhibits the transcriptional co-activator YAP and cell growth via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein kinases.

Proc Natl Acad Sci U S A. 2013-10-7

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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies.

Nat Genet. 2015-3

[2]
Poly-ADP ribosylation of PTEN by tankyrases promotes PTEN degradation and tumor growth.

Genes Dev. 2015-1-15

[3]
Energy stress regulates hippo-YAP signaling involving AMPK-mediated regulation of angiomotin-like 1 protein.

Cell Rep. 2014-10-23

[4]
KRAS and YAP1 converge to regulate EMT and tumor survival.

Cell. 2014-6-19

[5]
Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.

Cell. 2014-6-19

[6]
The Hippo signaling pathway in stem cell biology and cancer.

EMBO Rep. 2014-6

[7]
A peptide mimicking VGLL4 function acts as a YAP antagonist therapy against gastric cancer.

Cancer Cell. 2014-2-10

[8]
VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex.

Cell Res. 2014-3

[9]
Actin-binding and cell proliferation activities of angiomotin family members are regulated by Hippo pathway-mediated phosphorylation.

J Biol Chem. 2013-11-13

[10]
Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis.

J Biol Chem. 2013-10-8

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