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Speedy/RINGO protein interacts with ERK/MAPK and PI3K/AKT pathways in SH-SY5Y neuroblastoma cells

Yesim Kaya1, Seren Kucukvardar1,2, Aysegul Yildiz3

  • 1Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey.

Molecular and Cellular Biochemistry
|July 1, 2020
PubMed

Insights

This study reveals Speedy/RINGO interacts with ERK/MAPK and PI3K/AKT pathways in neuroblastoma cells. Inhibiting Speedy/RINGO or these pathways reduces cancer cell viability, suggesting new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Abnormal signaling in ERK/MAPK and PI3K/AKT pathways drives cancer, including neuroblastoma.
  • Cell cycle regulators like Speedy/RINGO are implicated in neuroblastoma development.
  • Existing research suggests crosstalk between ERK/MAPK, PI3K/AKT, and Speedy/RINGO in other cell types.

Purpose of the Study:

  • To investigate the interaction between Speedy/RINGO and the PI3K/AKT and ERK/MAPK pathways in SH-SY5Y neuroblastoma cells.
  • To determine the effect of Speedy/RINGO modulation on these critical signaling pathways.
  • To explore potential therapeutic strategies targeting these interactions in neuroblastoma.

Main Methods:

  • Silencing Speedy/RINGO using siRNA in SH-SY5Y neuroblastoma cells.
  • Inhibiting the MEK1/2 component of the ERK/MAPK pathway with U0126.
  • Analyzing changes in protein expression and phosphorylation (e.g., AKT phosphorylation).
  • Assessing cell viability using MTS assays.

Main Results:

  • Speedy/RINGO silencing led to decreased MEK1/2 expression and AKT phosphorylation.
  • Inhibition of MEK1/2 resulted in reduced Speedy/RINGO expression and AKT phosphorylation, indicating a reciprocal interaction.
  • Both Speedy/RINGO silencing and ERK/MAPK inhibition significantly decreased SH-SY5Y cell viability.

Conclusions:

  • This study demonstrates, for the first time, an interaction between Speedy/RINGO and the PI3K/AKT and ERK/MAPK pathways in neuroblastoma cells.
  • The findings highlight a reciprocal relationship between Speedy/RINGO and the ERK/MAPK pathway.
  • Targeting Speedy/RINGO or these signaling pathways holds promise for developing novel neuroblastoma treatments.
Keywords:
ERK/MAPKNeuroblastomaPI3K/AKTSH-SY5YSpeedy/RINGO

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