The Role of the ShcD and RET Interaction in Neuroblastoma Survival and Migration

Overview

Journal Biochem Biophys Rep

Specialty Biochemistry

Date 2018 Mar 21

PMID 29556564

Citations 2

Authors

Zeanap A Mabruk

Samrein B M Ahmed

Asha Caroline Thomas

Sally A Prigent

Affiliations

Soon will be listed here.

Abstract

Preliminary screening data showed that the ShcD adaptor protein associates with the proto-oncogene RET receptor tyrosine kinase. In the present study, we aimed to investigate the molecular interaction between ShcD and RET in human neuroblastoma cells and study the functional impact of this interaction. We were able to show that ShcD immunoprecipitated with RET from SK-N-AS neuroblastoma cell lysates upon GDNF treatment. This result was validated by ShcD-RET co-localization, which was visualized using a fluorescence microscope. ShcD-RET coexpression promoted ShcD and RET endosomal localization, resulting in unexpected inhibition of the downstream ERK and AKT pathways. Interestingly, ShcD-RET association reduced the viability and migration of SK-N-AS cells. Although ShcD was previously shown to trigger melanoma cell migration and tumorigenesis, our data showed an opposite role for ShcD in neuroblastoma SK-N-AS cells via its association with RET in GDNF-treated cells. In conclusion, ShcD acts as a switch molecule that promotes contrasting biological responses depending on the stimulus ad cell type.

Citing Articles

Targeting the RET tyrosine kinase in neuroblastoma: A review and application of a novel selective drug design strategy.

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Systematic review of the receptor tyrosine kinase superfamily in neuroblastoma pathophysiology.

Rozen E, Shohet J Cancer Metastasis Rev. 2021; 41(1):33-52.

PMID: 34716856 PMC: 8924100. DOI: 10.1007/s10555-021-10001-7.

References

Pellegrini M, Finetti F, Petronilli V, Ulivieri C, Giusti F, Lupetti P . p66SHC promotes T cell apoptosis by inducing mitochondrial dysfunction and impaired Ca2+ homeostasis. Cell Death Differ. 2006; 14(2):338-47. DOI: 10.1038/sj.cdd.4401997. View

Mulligan L . RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer. 2014; 14(3):173-86. DOI: 10.1038/nrc3680. View

Melillo R, Carlomagno F, De Vita G, Formisano P, Vecchio G, Fusco A . The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret. Oncogene. 2001; 20(2):209-18. DOI: 10.1038/sj.onc.1204049. View

B M Ahmed S, Prigent S . A nuclear export signal and oxidative stress regulate ShcD subcellular localisation: a potential role for ShcD in the nucleus. Cell Signal. 2013; 26(1):32-40. DOI: 10.1016/j.cellsig.2013.09.003. View

Li L, Su Y, Zhao C, Zhao H, Liu G, Wang J . The role of Ret receptor tyrosine kinase in dopaminergic neuron development. Neuroscience. 2006; 142(2):391-400. DOI: 10.1016/j.neuroscience.2006.06.018. View

Hawley S, Wills M, Rabalski A, Bendall A, Jones N . Expression patterns of ShcD and Shc family adaptor proteins during mouse embryonic development. Dev Dyn. 2010; 240(1):221-31. DOI: 10.1002/dvdy.22506. View

Bhat S, Anand D, Khanday F . p66Shc as a switch in bringing about contrasting responses in cell growth: implications on cell proliferation and apoptosis. Mol Cancer. 2015; 14:76. PMC: 4421994. DOI: 10.1186/s12943-015-0354-9. View

Ding X, Xiang L, Wang N, Zhao Z, Jin X, Sun Y . Vandetanib-induced inhibition of neuroblastoma cell migration and invasion is associated with downregulation of the SDF-1/CXCR4 axis and matrix metalloproteinase 14. Oncol Rep. 2014; 31(3):1165-74. DOI: 10.3892/or.2013.2963. View

Woldt E, Matz R, Terrand J, Mlih M, Gracia C, Foppolo S . Differential signaling by adaptor molecules LRP1 and ShcA regulates adipogenesis by the insulin-like growth factor-1 receptor. J Biol Chem. 2011; 286(19):16775-82. PMC: 3089520. DOI: 10.1074/jbc.M110.212878. View

10.

Panta G, Du L, Nwariaku F, Kim L . Direct phosphorylation of proliferative and survival pathway proteins by RET. Surgery. 2005; 138(2):269-74. DOI: 10.1016/j.surg.2005.04.007. View

11.

Soba P, Han C, Zheng Y, Perea D, Miguel-Aliaga I, Jan L . The Ret receptor regulates sensory neuron dendrite growth and integrin mediated adhesion. Elife. 2015; 4. PMC: 4391025. DOI: 10.7554/eLife.05491. View

12.

Lee M, Pardoux C, Hall M, Lee P, Warburton D, Qing J . TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007; 26(17):3957-67. PMC: 1994119. DOI: 10.1038/sj.emboj.7601818. View

13.

Bordeaux M, Forcet C, Granger L, Corset V, Bidaud C, Billaud M . The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung disease. EMBO J. 2000; 19(15):4056-63. PMC: 306592. DOI: 10.1093/emboj/19.15.4056. View

14.

Richardson D, Rodrigues D, Hyndman B, Crupi M, Nicolescu A, Mulligan L . Alternative splicing results in RET isoforms with distinct trafficking properties. Mol Biol Cell. 2012; 23(19):3838-50. PMC: 3459860. DOI: 10.1091/mbc.E12-02-0114. View

15.

Jones N, Hardy W, Friese M, Jorgensen C, Smith M, Woody N . Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase. Mol Cell Biol. 2007; 27(13):4759-73. PMC: 1951494. DOI: 10.1128/MCB.00184-07. View

16.

Pasini L, Turco M, Luzi L, Aladowicz E, Fagiani E, Lanfrancone L . Melanoma: targeting signaling pathways and RaLP. Expert Opin Ther Targets. 2008; 13(1):93-104. DOI: 10.1517/14728220802607363. View

17.

Xi G, Shen X, Clemmons D . p66shc negatively regulates insulin-like growth factor I signal transduction via inhibition of p52shc binding to Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 leading to impaired growth factor receptor-bound protein-2.... Mol Endocrinol. 2008; 22(9):2162-75. PMC: 2631373. DOI: 10.1210/me.2008-0079. View

18.

Smith M, Hardy W, Murphy J, Jones N, Pawson T . Screening for PTB domain binding partners and ligand specificity using proteome-derived NPXY peptide arrays. Mol Cell Biol. 2006; 26(22):8461-74. PMC: 1636785. DOI: 10.1128/MCB.01491-06. View

19.

Lemmon M, Schlessinger J . Cell signaling by receptor tyrosine kinases. Cell. 2010; 141(7):1117-34. PMC: 2914105. DOI: 10.1016/j.cell.2010.06.011. View

20.

Richardson D, Lai A, Mulligan L . RET ligand-induced internalization and its consequences for downstream signaling. Oncogene. 2006; 25(22):3206-11. DOI: 10.1038/sj.onc.1209349. View