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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...
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The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
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Related Experiment Video

Updated: May 28, 2026

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix
08:49

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix

Published on: July 10, 2016

PI3K/mTOR signaling regulates prostatic branching morphogenesis.

Susmita Ghosh1, Hiu Lau, Brian W Simons

  • 1Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.

Developmental Biology
|October 22, 2011
PubMed
Summary
This summary is machine-generated.

The PI3K/mTOR pathway is crucial for prostate development, regulating epithelial cell migration and invasion. Its precise balance, particularly mTORC1 activity, is key for proper prostatic branching morphogenesis.

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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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Last Updated: May 28, 2026

Engineering Three-dimensional Epithelial Tissues Embedded within Extracellular Matrix
08:49

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Published on: July 10, 2016

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

Area of Science:

  • Urology
  • Developmental Biology
  • Cell Signaling

Background:

  • Prostatic branching morphogenesis is complex, involving hormonal and growth factor signaling.
  • Downstream pathways orchestrating this process are not well understood.

Purpose of the Study:

  • Investigate the role of PI3K and mTOR signaling in prostatic organogenesis.
  • Elucidate the cellular mechanisms of PI3K/mTOR in prostatic development.

Main Methods:

  • Utilized a mesenchyme-free embryonic prostate culture system.
  • Employed novel mTOR inhibitors and a conditional PTEN loss-of-function model.
  • Analyzed PI3K/mTOR activity during murine prostatic development.

Main Results:

  • Androgen robustly induces PI3K/mTOR activity, essential for epithelial bud invasion.
  • PI3K/mTOR inhibition impairs epithelial cell migration but not proliferation or apoptosis.
  • Simultaneous mTORC1/mTORC2 inhibition phenocopies PI3K/mTOR inhibition; mTORC1 inhibition alone increases branching.
  • PTEN loss-of-function decreases budding, reversible by mTORC1 inhibition.

Conclusions:

  • PI3K/mTOR signaling is vital for prostatic epithelial invasion and migration.
  • The balance of PI3K and downstream mTORC1/C2 activity critically regulates prostatic morphogenesis.