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Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK

Han C Dan1, Matthew J Cooper, Patricia C Cogswell

  • 1Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.

Genes & Development
|June 4, 2008
PubMed

Insights

The mammalian target of rapamycin (mTOR) pathway, downstream of Akt, controls nuclear factor kappa B (NF-kappaB) activity in prostate cancer. Rapamycin inhibits this pathway, offering therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nuclear factor kappa B (NF-kappaB) plays a crucial role in cancer development and progression.
  • The serine-threonine kinase Akt is a key oncoprotein activated in various cancers.
  • Mammalian target of rapamycin (mTOR) is a key effector of Akt-induced signaling.

Purpose of the Study:

  • To elucidate the mechanisms of NF-kappaB activation in cancer.
  • To investigate the role of the Akt/mTOR pathway in regulating NF-kappaB activity.
  • To understand the therapeutic action of rapamycin in PTEN-deficient prostate cancer.

Main Methods:

  • Investigated the interaction between mTOR, Akt, and NF-kappaB signaling.
  • Utilized PTEN-null/inactive prostate cancer cells.
  • Assessed the effect of the mTOR inhibitor rapamycin on IKK activity.

Main Results:

  • mTOR, downstream of Akt, controls NF-kappaB activity via IKK stimulation in PTEN-deficient prostate cancer cells.
  • The mTOR-associated protein Raptor is essential for Akt-induced NF-kappaB activation.
  • Rapamycin suppresses IKK activity in PTEN-deficient prostate cancer cells, potentially by dissociating Raptor from mTOR.

Conclusions:

  • The Akt/mTOR pathway significantly influences NF-kappaB-dependent gene expression in prostate cancer.
  • Rapamycin demonstrates therapeutic potential by inhibiting the Akt/mTOR/NF-kappaB signaling axis.
  • These findings provide insights into cancer mechanisms and rapamycin's therapeutic effects.

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