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The role of the ShcD and RET interaction in neuroblastoma survival and migration

Zeanap A Mabruk1, Samrein B M Ahmed1, Asha Caroline Thomas1

  • 1Sharjah Institute for Medical Research and College of Medicine University of Sharjah, United Arab Emirates.

Biochemistry and Biophysics Reports
|March 21, 2018
PubMed

Insights

The ShcD adaptor protein interacts with the RET receptor tyrosine kinase in neuroblastoma cells, inhibiting cell viability and migration. This study reveals ShcD

Area of Science:

  • Molecular biology
  • Cell biology
  • Oncology

Background:

  • The ShcD adaptor protein is known to associate with the proto-oncogene RET receptor tyrosine kinase.
  • Understanding the interaction between ShcD and RET is crucial for neuroblastoma research.

Purpose of the Study:

  • To investigate the molecular interaction between ShcD and RET in human neuroblastoma cells.
  • To elucidate the functional impact of ShcD-RET interaction on neuroblastoma cell behavior.

Main Methods:

  • Co-immunoprecipitation assays to confirm ShcD-RET association.
  • Fluorescence microscopy for ShcD-RET co-localization studies.
  • Analysis of downstream signaling pathways (ERK, AKT) and cell viability/migration assays.

Main Results:

  • ShcD immunoprecipitated with RET in SK-N-AS neuroblastoma cells upon GDNF treatment.
  • ShcD-RET co-expression led to endosomal localization and inhibition of ERK and AKT pathways.
  • ShcD-RET association reduced neuroblastoma cell viability and migration.

Conclusions:

  • ShcD acts as a switch molecule, exhibiting contrasting biological roles in different cell types and contexts.
  • ShcD-RET interaction inhibits neuroblastoma cell viability and migration, opposing its previously observed role in melanoma.
  • This interaction presents a potential therapeutic target for neuroblastoma treatment.
Keywords:
ALK,, Anaplastic Lymphoma KinaseAkt,, Protein kinase B;CMV,, CytomegalovirusDMEM,, Dulbecoo Modified Eagle's Medium;DNA,, Deoxyribonucleic AcidECL,, Enhanced Chemiluminescence;EGF,, Epidermal Growth Factor;EGFR,, Epidermal Growth Factor Receptor;ERK,, Extracellular Signal–Regulated Kinases;EndosomesFBS,, Fetal Bovine SerumFGFR,, fibroblast growth factor receptorsGDNFGDNF,, Glial Cell Line-Derived Neurotropic Factor;GFLs,, GDNF Family Ligands;GFP,, Green Fluorescent ProteinGPCR,, G-Protein Coupled ReceptorGRB2,, Growth Factor Receptor-Bound Protein 2;HGFR,, hepatocyte growth factor receptor;HRP,, Horseradish PeroxidaseIGF,, Insulin Growth Factor;LB,, Luria-BertaniMAP,, Mitogen-Activated Protein;MAPK,, Mitogen-Activated Protein KinasesMuSK,, Muscle Specific KinaseNFDM,, Non-Fat Dry MilkNeuroblastomaPBS,, Phosphate-Buffered SalinePBST,, Phosphate-Buffered Saline TweenPDGF,, Platelet-Derived Growth Factor;PI3K,, Phosphoinositide 3-KinasePMSF,, Phenylmethylsulfonyl FluoridePVDF,, Polyvinylidene FluorideRETRET,, Rearranged During TransfectionRT,, Room Temperature;RTKs,, Receptor Tyrosine KinaseSDS-PAGE,, Sodium Dodecylsulphate Polyacrylamide Gel ElectrophoresisShcDShcD,, Src Homology And Collagen DSrc,, Proto-Oncogene Tyrosine-Protein Kinase SrcTKRs,, Tyrosine Kinase Receptor;TrkA/B/C,, Tropomyosin-Related Kinase Receptor A/B/Chrs,, HoursmAb,, Monoclonal Antibodymin,, MinutepAb,, Polyclonal AntibodypTyr,, Phospho-Tyrosinerpm,, revolution per minute;

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