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Related Experiment Video

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Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

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Novel PP2A-Activating Compounds in Neuroblastoma.

Nazia Nazam¹, Laura V Bownes¹, Janet R Julson¹

¹Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

|November 27, 2024

Summary

Novel protein phosphatase 2A (PP2A) activators show promise in treating neuroblastoma (NB). These compounds reduced NB cell growth and tumor development, particularly in MYCN-amplified tumors.

Keywords:

ATUX-3364 ATUX-8385 neuroblastoma protein phosphatase 2A

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Published on: August 25, 2021

Area of Science:

Oncology
Molecular Biology
Pediatric Medicine

Background:

Neuroblastoma (NB) is a deadly pediatric cancer with poor prognosis for high-risk patients.
Protein phosphatase 2A (PP2A), a tumor suppressor, is downregulated in NB.
Targeting PP2A is a potential therapeutic strategy for NB.

Purpose of the Study:

To investigate the therapeutic potential of two novel PP2A activators, ATUX-3364 and ATUX-8385, for neuroblastoma treatment.
To explore the effects of PP2A activation on NB cell behavior and tumor growth.

Main Methods:

Utilized four NB cell lines and a patient-derived xenograft model.
Assessed effects on cell viability, proliferation, and motility.
Evaluated in vivo tumor growth and molecular mechanisms.

Main Results:

ATUX-3364 and ATUX-8385 enhanced PP2A activity, decreasing NB cell viability, proliferation, and motility.
In vivo studies showed reduced tumor growth in MYCN-amplified NB xenografts.
Treatment led to decreased MYCN protein expression via dephosphorylation of MYCN-S62.

Conclusions:

PP2A activators demonstrate efficacy in reducing NB cell growth and motility.
Significant anti-tumor effects were observed in MYCN-amplified NB models.
PP2A activation targets MYCN, offering a potential therapeutic avenue for NB treatment.