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Tumor Biology
Published in: Tumor Biology 4/2015

01-04-2015 | Review

Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects

Authors: Yong-Chang Liu, Yan-zhou Wang

Published in: Tumor Biology | Issue 4/2015

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Abstract

The activation of proline-rich phosphoprotein Yes-associated protein 1 (YAP1) possesses a possible link between stem/progenitor cells, organ size, and cancer. YAP1 has been indicated as an oncoprotein, and overexpression of YAP1 is reported in many human brain tumors, including infiltrating gliomas. During normal brain development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in neural progenitor cells to promote guidepost cell differentiation, but loss of NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts guidepost formation. Overexpression of endogenous CD44 (cancer stem cell marker) promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and leads to cancer cell resistance in glioblastoma. The hippo pathway is also related to the YAP1 action. However, the mechanism of YAP1 action in glioma is still far from clear understanding. Advances in clinical management based on an improved understanding of the function of YAP1 may help to serve as a molecular target in glioma therapeutics. Knockdown of YAP1 by shRNA technology has been shown to reduce glioma in vitro; however, clinical implications are still under investigation. YAP1 can be used as a diagnostic marker for gliomas to monitor the disease status and may help to evaluate its treatment effects. More functional experiments are needed to support the direct roles of YAP1 on gliomas at molecular and cellular levels.
Literature
1.
Sudol M. Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene. 1994;9:2145–52.PubMed
2.
Sudol M, Bork P, Einbond A, Kastury K, Druck T, Negrini M, et al. Characterization of the mammalian YAP (Yes-associated protein) gene and its role in defining a novel protein module, the WW domain. J Biol Chem. 1995;270:14733–41.CrossRefPubMed
3.
Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003;278:33334–41.CrossRefPubMed
4.
Espanel X, Sudol M. Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. J Biol Chem. 2001;276:14514–23.PubMed
5.
Iwasa H, Maimaiti S, Kuroyanagi H, Kawano S, Inami K, Timalsina S, et al. Yes-associated protein homolog, YAP-1, is involved in the thermotolerance and aging in the nematode Caenorhabditis elegans. Exp Cell Res. 2013;319:931–45.CrossRefPubMed
6.
Zhao B, Li L, Lu Q, Wang LH, Liu CY, Lei Q, et al. Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. Genes Dev. 2011;25:51–63.CrossRefPubMedPubMedCentral
7.
8.
Camargo FD, Gokhale S, Johnnidis JB, Fu D, Bell GW, Jaenisch R, et al. YAP1 increases organ size and expands undifferentiated progenitor cells. Curr Biol. 2007;17:2054–60.CrossRefPubMed
9.
10.
Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA, et al. Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell. 2007;130:1120–33.CrossRefPubMedPubMedCentral
11.
12.
13.
Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, et al. Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001;15:1311–33.CrossRefPubMed
14.
Bleeker FE, Molenaar RJ, Leenstra S. Recent advances in the molecular understanding of glioblastoma. J Neuro-Oncol. 2012;108:11–27.CrossRef
15.
Reuss D, von Deimling A. Hereditary tumor syndromes and gliomas. Recent Results Cancer Res. 2009;171:83–102.CrossRefPubMed
16.
Adel Fahmideh M, Schwartzbaum J, Frumento P, Feychting M. Association between DNA repair gene polymorphisms and risk of glioma: a systematic review and meta-analysis. Neuro-Oncol. 2014;16:807–14.CrossRefPubMedPubMedCentral
17.
Steinhardt AA, Gayyed MF, Klein AP, Dong J, Maitra A, Pan D, et al. Expression of Yes-associated protein in common solid tumors. Hum Pathol. 2008;39:1582–9.CrossRefPubMedPubMedCentral
18.
Cao JJ, Zhao XM, Wang DL, Chen KH, Sheng X, Li WB, et al. YAP is overexpressed in clear cell renal cell carcinoma and its knockdown reduces cell proliferation and induces cell cycle arrest and apoptosis. Oncol Rep. 2014;32:1594–600.PubMed
19.
Xu MZ, Yao TJ, Lee NP, Ng IO, Chan YT, Zender L, et al. Yes-associated protein is an independent prognostic marker in hepatocellular carcinoma. Cancer. 2009;115:4576–85.CrossRefPubMedPubMedCentral
20.
Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, et al. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci U S A. 2006;103:12405–10.CrossRefPubMedPubMedCentral
21.
Zhao B, Wei X, Li W, Udan RS, Yang Q, Kim J, et al. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes Dev. 2007;21:2747–61.CrossRefPubMedPubMedCentral
22.
Orr BA, Bai H, Odia Y, Jain D, Anders RA, Eberhart CG. Yes-associated protein 1 is widely expressed in human brain tumors and promotes glioblastoma growth. J Neuropathol Exp Neurol. 2011;70:568–77.CrossRefPubMedPubMedCentral
23.
Li SY, Hu JA, Wang HM. Expression of Yes-associated protein 1 gene and protein in oral squamous cell carcinoma. Chin Med J (Engl). 2013;126:655–8.
24.
Fernandez-L A, Northcott PA, Dalton J, Fraga C, Ellison D, Angers S, et al. YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes Dev. 2009;23:2729–41.CrossRefPubMedPubMedCentral
25.
Baia GS, Caballero OL, Orr BA, Lal A, Ho JS, Cowdrey C, et al. Yes-associated protein 1 is activated and functions as an oncogene in meningiomas. Mol Cancer Res. 2012;10:904–13.CrossRefPubMedPubMedCentral
26.
Modena P, Lualdi E, Facchinetti F, Veltman J, Reid JF, Minardi S, et al. Identification of tumor-specific molecular signatures in intracranial ependymoma and association with clinical characteristics. J Clin Oncol. 2006;24:5223–33.CrossRefPubMed
27.
Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110.CrossRefPubMedPubMedCentral
28.
29.
Zeng Q, Hong W. The emerging role of the Hippo pathway in cell contact inhibition, organ size control, and cancer development in mammals. Cancer Cell. 2008;13:188–92.CrossRefPubMed
30.
Huang J, Wu S, Barrera J, Matthews K, Pan D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. Cell. 2005;122:421–34.CrossRefPubMed
31.
Harvey KF, Zhang X, Thomas DM. The Hippo pathway and human cancer. Nat Rev Cancer. 2013;13:246–57.CrossRefPubMed
32.
Nishio M, Otsubo K, Maehama T, Mimori K, Suzuki A. Capturing the mammalian Hippo: elucidating its role in cancer. Cancer Sci. 2013;104:1271–7.CrossRefPubMed
33.
Hong W, Guan KL. The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway. Semin Cell Dev Biol. 2012;23:785–93.CrossRefPubMedPubMedCentral
34.
Wang W, Huang J, Chen J. Angiomotin-like proteins associate with and negatively regulate YAP1. J Biol Chem. 2011;286:4364–70.CrossRefPubMed
35.
Chan SW, Lim CJ, Chong YF, Pobbati AV, Huang C, Hong W. Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J Biol Chem. 2011;286:7018–26.CrossRefPubMedPubMedCentral
36.
Zhao B, Li L, Tumaneng K, Wang CY, Guan KL. A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF (beta-TRCP). Genes Dev. 2010;24:72–85.CrossRefPubMedPubMedCentral
37.
Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev. 2014;94:1287–312.CrossRefPubMed
38.
Lei QY, Zhang H, Zhao B, Zha ZY, Bai F, Pei XH, et al. TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the Hippo pathway. Mol Cell Biol. 2008;28:2426–36.CrossRefPubMedPubMedCentral
39.
Zhang X, Milton CC, Humbert PO, Harvey KF. Transcriptional output of the Salvador/Warts/Hippo pathway is controlled in distinct fashions in Drosophila melanogaster and mammalian cell lines. Cancer Res. 2009;69:6033–41.CrossRefPubMed
40.
Alonso ME, Bello MJ, Arjona D, Gonzalez-Gomez P, Lomas J, de Campos JM, et al. Analysis of the NF2 gene in oligodendrogliomas and ependymomas. Cancer Genet Cytogenet. 2002;134:1–5.CrossRefPubMed
41.
Zhang N, Bai H, David KK, Dong J, Zheng Y, Cai J, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19:27–38.CrossRefPubMedPubMedCentral
42.
Striedinger K, VandenBerg SR, Baia GS, McDermott MW, Gutmann DH, Lal A. The neurofibromatosis 2 tumor suppressor gene product, merlin, regulates human meningioma cell growth by signaling through YAP. Neoplasia. 2008;10:1204–12.CrossRefPubMedPubMedCentral
43.
Lavado A, Ware M, Paré J, Cao X. The tumor suppressor Nf2 regulates corpus callosum development by inhibiting the transcriptional coactivator Yap. Development. 2014;141:4182–93.CrossRefPubMedPubMedCentral
44.
Xu Y, Stamenkovic I, Yu Q. CD44 attenuates activation of the Hippo signaling pathway and is a prime therapeutic target for glioblastoma. Cancer Res. 2010;70:2455–64.CrossRefPubMedPubMedCentral
45.
Jiang Z, Li X, Hu J, Zhou W, Jiang Y, Li G, et al. Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neurosci Res. 2006;56:450–8.CrossRefPubMed
46.
Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–8.CrossRef
47.
48.
Frattini V, Trifonov V, Chan JM, Castano A, Lia M, Abate F, et al. The integrated landscape of driver genomic alterations in glioblastoma. Nat Genet. 2013;45:1141–9.CrossRefPubMedPubMedCentral
49.
Dixit D, Ghildiyal R, Anto NP, Sen E. Chaetocin-induced ROS-mediated apoptosis involves ATM-YAP1 axis and JNK-dependent inhibition of glucose metabolism. Cell Death Dis. 2014;5:e1212.CrossRefPubMedPubMedCentral
50.
Okazaki T, Kageji T, Kuwayama K, Kitazato KT, Mure H, Hara K, et al. Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma. Cancer Lett. 2012;323:199–207.CrossRefPubMed
Metadata
Title
Role of Yes-associated protein 1 in gliomas: pathologic and therapeutic aspects
Authors
Yong-Chang Liu
Yan-zhou Wang
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3297-2

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