Related Experiment Video

Updated: Feb 11, 2026

Enumeration of Neural Stem Cells Using Clonal Assays
10:32

Enumeration of Neural Stem Cells Using Clonal Assays

Published on: October 4, 2016

8.8K

PI3K activation in neural stem cells drives tumorigenesis which can be ameliorated by targeting the cAMP response

Paul M Daniel1, Gulay Filiz1, Daniel V Brown1

  • 1Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.

Neuro-Oncology
|May 3, 2018
PubMed
Abstract

Insights

Hyperactivation of phosphoinositide 3-kinase (PI3K) signaling drives glioma development. Disrupting downstream cAMP response element binding protein (CREB) signaling in PI3K-mutant tumors extended symptom-free survival in mice.

Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • Aberrant phosphoinositide 3-kinase (PI3K) signaling is prevalent in various cancers, including glioma.
  • The exact role of PI3K signaling in glioma pathogenesis is not fully understood.
  • Studies in neural stem/progenitor cells (NSPCs) offer insights into PI3K pathway cooperation with other signaling cascades in brain cancer.

Purpose of the Study:

  • To elucidate the function of the PI3K pathway in glioma initiation and progression.
  • To establish a novel mouse model for studying glioma development driven by PI3K pathway alterations.

Main Methods:

  • Generated a mouse model with inducible expression of a PIK3CA oncogenic mutant (H1047A) and deletion of the phosphatase and tensin homolog (PTEN) in NSPCs.
  • Investigated tumor formation, cellular characteristics, and signaling pathway alterations in the developed mouse model.

Main Results:

  • Expression of PIK3CAH1047A alone induced oligodendroglial tumors.
  • Simultaneous loss of PTEN was essential for the development of invasive, high-grade gliomas.
  • PI3K-mutant NSPCs showed increased neurosphere formation linked to Wnt signaling activation.
  • Loss of cAMP response element binding protein (CREB) in PI3K-PTEN mutant tumors resulted in prolonged symptom-free survival.

Conclusions:

  • The PI3K pathway is critical for glioma initiation.
  • Targeting downstream CREB signaling can attenuate tumor expansion and potentially improve therapeutic outcomes in glioma.

More Related Videos

Classification of Neural Stem Cell Activation State In Vitro using Autofluorescence06:56

Classification of Neural Stem Cell Activation State In Vitro using Autofluorescence

Published on: April 12, 2024

1.0K
Culturing Human Pluripotent and Neural Stem Cells in an Enclosed Cell Culture System for Basic and Preclinical Research08:05

Culturing Human Pluripotent and Neural Stem Cells in an Enclosed Cell Culture System for Basic and Preclinical Research

Published on: June 10, 2016

11.0K

Related Concept Videos

Target Cell Response to Hormones01:22

Target Cell Response to Hormones

Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
5.8K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.6K
Classification of Elements and Compounds02:54

Classification of Elements and Compounds

Pure substances consist of only one type of matter. A pure substance can be an element or a compound. An element consists of only one type of atom, while a compound consists of two or more types of atoms held together by a chemical bond. Elements are classified as atomic or molecular based on the nature of their basic units.
Compounds are pure substances composed of two or more elements in fixed, definite proportions. Compounds are classified as ionic or molecular (covalent) based on the bonds...
73.4K
Elements and Compounds01:27

Elements and Compounds

Pure substances consist of only one type of matter. A pure substance can be an element or a compound. An element consists of only one type of atom, while a compound consists of two or more types of atoms held together by a chemical bond.
Elements
Elements are classified as atomic or molecular based on the nature of their basic units. They are unique forms of matter with specific chemical and physical properties that cannot break down into smaller substances by ordinary chemical reactions. There...
105.3K
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
8.7K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
5.6K