Related Experiment Video

Updated: May 14, 2026

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration
11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

FOXO3a is a major target of inactivation by PI3K/AKT signaling in aggressive neuroblastoma

Evan E Santo1, Peter Stroeken, Peter V Sluis

  • 1Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Cancer Research
|February 5, 2013
PubMed

Insights

The phosphoinositide 3-kinase (PI3K)/AKT pathway drives neuroblastoma growth by inactivating the FOXO3a transcription factor. Restoring FOXO3a function induces apoptosis, offering a potential therapeutic strategy for this pediatric cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Neuroblastoma is a pediatric cancer with unpredictable outcomes.
  • The PI3K/AKT pathway is frequently activated in neuroblastoma, correlating with poor prognosis.
  • Downstream targets of PI3K/AKT in neuroblastoma remain largely unknown.

Purpose of the Study:

  • To identify key downstream effectors of the PI3K/AKT pathway in neuroblastoma.
  • To investigate the role of the transcription factor FOXO3a in neuroblastoma.
  • To evaluate FOXO3a as a prognostic marker and a predictive biomarker for PI3K/AKT inhibitors.

Main Methods:

  • Analysis of FOXO3a expression in neuroblastoma cell lines and clinical specimens.
  • Investigating the effect of PI3K/AKT pathway inhibitors (PI-103, MK-2206) on FOXO3a activity and apoptosis.
  • Gene expression analysis to correlate PI3K signaling and FOXO3a activity with patient prognosis.

Main Results:

  • FOXO3a expression is inversely correlated with neuroblastoma stage and PI3K/AKT pathway activation.
  • AKT-mediated inactivation of FOXO3a is crucial for neuroblastoma cell survival.
  • PI3K/AKT inhibition activates FOXO3a, leading to apoptosis, which can be modulated by FOXO3a levels.
  • High PI3K activity and low FOXO3a activity are associated with poor prognosis in neuroblastoma patients.

Conclusions:

  • FOXO3a is a critical downstream target of the PI3K/AKT pathway in neuroblastoma.
  • FOXO3a expression serves as a prognostic indicator and a potential biomarker for predicting response to PI3K/AKT inhibitors.
  • Targeting the PI3K/AKT/FOXO3a axis presents a promising therapeutic avenue for neuroblastoma.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...