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Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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.
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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
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Related Experiment Video

Updated: Jan 27, 2026

Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation
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Gamma-Tocotrienol Induces Apoptosis in Prostate Cancer Cells by Targeting the Ang-1/Tie-2 Signalling Pathway.

Kai Dun Tang1, Ji Liu2, Pamela J Russell3

  • 1The School of Biomedical Sciences, Australian Prostate Cancer Research Centre-Queensland & Institute of Health and Biomedical Innovation, Queensland University of Technology and The Translational Research Institute, Queensland 4102, Australia. kai.tang@qut.edu.au.

International Journal of Molecular Sciences
|March 15, 2019
PubMed
Summary

Gamma-tocotrienol (γ-T3), a vitamin E form, shows anti-cancer effects by targeting cancer stem cells. It suppresses Angiopoietin-1 (Ang-1) and enhances γ-T3

Keywords:
Tie-2angiopoietin-1gamma-tocotrienol and autophagyprostate cancer

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Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Gamma-tocotrienol (γ-T3), a vitamin E isomer, exhibits broad-spectrum anti-cancer properties.
  • γ-T3 demonstrates efficacy in inhibiting cancer cell growth, angiogenesis, metastasis, and targeting cancer stem cells (CSCs).
  • The precise molecular mechanisms underlying γ-T3's anti-cancer effects remain largely unelucidated.

Purpose of the Study:

  • To identify novel downstream targets of γ-T3 in cancer.
  • To investigate the role of the Angiopoietin-1 (Ang-1)/Tie-2 pathway in γ-T3's anti-cancer activity.
  • To explore the therapeutic potential of combining γ-T3 with Tie-2 inhibitors.

Main Methods:

  • Prostate cancer cell lines were treated with γ-T3.
  • Angiopoietin-1 (Ang-1) and Tie-2 expression levels were analyzed at mRNA and protein levels.
  • Functional assays were performed to assess the effects of Ang-1 supplementation and Tie-2 inactivation on γ-T3's anti-cancer activity.
  • AMP-activated protein kinase (AMPK) activation and autophagy were evaluated.

Main Results:

  • γ-T3 treatment suppressed Ang-1 expression in prostate cancer cells.
  • Ang-1 supplementation protected cancer cells from γ-T3's anti-CSC effects.
  • Inactivation of Tie-2 potentiated γ-T3's cytotoxic effects.
  • Tie-2 inactivation led to AMPK activation and autophagy interruption, enhancing γ-T3's efficacy.

Conclusions:

  • Angiopoietin-1/Tie-2 signaling is a novel downstream target pathway for γ-T3.
  • γ-T3 exhibits anti-cancer effects partly through the modulation of Ang-1/Tie-2 signaling.
  • Combination therapy of γ-T3 with Tie-2 inhibitors may represent a promising strategy for advanced prostate cancer treatment.