Related Experiment Video

Updated: Aug 21, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Rapamycin inhibits Akt-mediated oncogenic transformation and tumor growth

Xuesong Liu1, Jessica Powlas, Yan Shi

  • 1Cancer Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA.

Anticancer Research
|November 3, 2004
PubMed

Insights

The mTOR-p70S6K pathway is crucial for Akt-driven cell transformation and tumor formation. Inhibiting this pathway with rapamycin effectively blocks Akt-mediated growth in both cell cultures and animal models.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Akt (also known as Protein Kinase B) is a key regulator of cell survival and proliferation.
  • Upregulation of Akt isoforms is frequently observed in various human cancers.
  • Understanding the downstream pathways mediating Akt's oncogenic potential is critical for developing targeted therapies.

Purpose of the Study:

  • To investigate the specific signaling pathways required for Akt-mediated cellular transformation.
  • To determine the role of the mTOR-p70S6K, MAPK, and p38 MAPK pathways in Akt-driven oncogenesis.
  • To evaluate the therapeutic potential of inhibiting these pathways in preclinical models.

Main Methods:

  • Generation of NIH-3T3 cell lines overexpressing constitutively active Myr-Akt1 or Myr-Akt2.
  • Assessment of anchorage-independent growth using soft-agar assays.
  • In vivo tumor formation studies in SCID mice.
  • Pharmacological inhibition of the mTOR-p70S6K pathway using rapamycin.

Main Results:

  • NIH-3T3 cells overexpressing Myr-Akt1 or Myr-Akt2 exhibited anchorage-independent growth and tumor formation.
  • Rapamycin treatment significantly inhibited the activation of the mTOR-p70S6K pathway.
  • Rapamycin effectively suppressed anchorage-independent growth and tumor formation driven by Akt1 and Akt2.
  • The MAPK and p38 MAPK pathways were not essential for Akt-dependent transformation.

Conclusions:

  • The mTOR-p70S6K signaling pathway is a critical mediator of Akt-induced cellular transformation and tumorigenesis.
  • Targeting the mTOR-p70S6K pathway with rapamycin demonstrates significant anti-tumor activity in preclinical models.
  • These findings highlight the mTOR-p70S6K pathway as a promising therapeutic target for Akt-driven malignancies.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

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...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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.
The mTOR pathway or the...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...