Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell

A Silva1, A Gírio, I Cebola

  • 1Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.

Leukemia
|April 2, 2011
PubMed

Insights

Interleukin-7 (IL-7) signaling promotes T-cell acute lymphoblastic leukemia (T-ALL) survival by increasing reactive oxygen species (ROS) through the PI3K/Akt/mTOR pathway and glucose uptake. This pathway crosstalk presents a potential therapeutic target for T-ALL.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Interleukin-7 (IL-7) is crucial for T-cell development and survival.
  • The phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway regulates cell viability and proliferation.
  • T-cell acute lymphoblastic leukemia (T-ALL) cells rely on IL-7 for survival.

Purpose of the Study:

  • To investigate the role of reactive oxygen species (ROS) in IL-7-mediated T-ALL cell survival.
  • To elucidate the relationship between IL-7 signaling, ROS production, and glucose metabolism in T-ALL.

Main Methods:

  • Analysis of ROS production in T-ALL cells stimulated with IL-7.
  • Assessment of PI3K/Akt/mTOR pathway activity and its dependence on ROS and mitochondrial respiration.
  • Inhibition of glucose transporter (Glut) function using phloretin to evaluate its impact on ROS upregulation.

Main Results:

  • IL-7 upregulates ROS in T-ALL cells via PI3K/Akt/mTOR pathway activation, involving NADPH oxidase and mitochondrial respiration.
  • IL-7-induced PI3K activation requires mitochondrial respiration and ROS.
  • Glucose uptake, mediated by Glut1 upregulation, is essential for IL-7-induced ROS production in T-ALL cells.

Conclusions:

  • A critical crosstalk exists between the PI3K/Akt signaling pathway and ROS in IL-7-mediated T-ALL cell survival.
  • This interplay involves IL-7-driven PI3K activation, subsequent Glut1 upregulation, increased glucose uptake, and ROS generation.
  • The identified signaling axis represents a potential novel therapeutic target for T-ALL treatment.

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