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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...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Related Experiment Video

Updated: Jul 10, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

NOTCH and PI3K-AKT pathways intertwined.

Alejandro Gutierrez1, A Thomas Look

  • 1Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.

Cancer Cell
|November 13, 2007
PubMed
Summary

NOTCH1 signaling drives T cell acute lymphoblastic leukemia (T-ALL). Loss of PTEN confers resistance to NOTCH inhibition, shifting cancer dependence to the PI3K/AKT pathway, necessitating dual-pathway blockade for effective T-ALL treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Constitutive NOTCH1 receptor signaling is a key driver in over 50% of T cell acute lymphoblastic leukemia (T-ALL) cases.
  • Gamma-secretase inhibitors (GSIs) targeting NOTCH1 activation are ineffective in some T-ALL cell lines with mutated NOTCH1.
  • This resistance highlights a gap in current therapeutic strategies for T-ALL.

Purpose of the Study:

  • To investigate the mechanisms underlying resistance to NOTCH inhibition in T-ALL.
  • To identify alternative oncogenic pathways that confer resistance.
  • To propose novel therapeutic strategies for T-ALL treatment.

Main Methods:

  • Analysis of T-ALL cell lines with varying NOTCH1 and PTEN status.
  • Assessment of NOTCH1 and PI3K/AKT pathway signaling.

More Related Videos

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

Related Experiment Videos

Last Updated: Jul 10, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands
05:48

Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with Trans-Ligands and its Inhibition by Cis-Ligands

Published on: January 2, 2018

  • Evaluation of drug sensitivity to NOTCH inhibitors and PI3K/AKT pathway inhibitors.

    • Main Results:

    • Loss of PTEN was identified as a critical factor conferring resistance to NOTCH inhibition in T-ALL.
    • Loss of PTEN leads to the activation of the PI3K/AKT pathway, creating an "oncogene addiction" to this pathway.
    • Simultaneous inhibition of NOTCH1 and PI3K/AKT pathways demonstrated enhanced efficacy in resistant T-ALL models.

    Conclusions:

    • PTEN loss is a key mechanism of resistance to NOTCH-targeted therapy in T-ALL.
    • The PI3K/AKT pathway becomes a critical dependency in PTEN-deficient T-ALL.
    • Combined NOTCH and PI3K/AKT pathway inhibition represents a promising therapeutic approach for T-ALL patients with PTEN loss.