Related Experiment Video

Updated: Apr 28, 2026

Live-Cell Förster Resonance Energy Transfer Imaging of Metabolically Regulated Akt Activation Dynamics in HepG2 Cells
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Live-Cell Förster Resonance Energy Transfer Imaging of Metabolically Regulated Akt Activation Dynamics in HepG2 Cells

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Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3

Quanri Jin1, Hyo-Jong Lee2, Hye-Young Min3

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Carcinogenesis
|June 20, 2014
PubMed

Insights

Akt3 negatively regulates insulin-like growth factor binding protein-3 (IGFBP-3) in non-small cell lung cancer (NSCLC). Suppressing Akt3 enhances IGFBP-3 stability and antitumor activity, suggesting combined therapy for NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Insulin-like growth factor binding protein-3 (IGFBP-3) exhibits antitumor properties in non-small cell lung cancer (NSCLC).
  • The regulatory mechanisms of IGFBP-3 expression in NSCLC remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of Akt signaling pathway in regulating IGFBP-3 expression and activity in NSCLC.
  • To determine the specific Akt subtype involved in IGFBP-3 regulation.

Main Methods:

  • Utilized genomic and pharmacologic approaches to activate or suppress Akt signaling in NSCLC cell lines.
  • Employed constitutively active Akt subtypes (HA-Akt-DD) to assess individual subtype contributions.
  • Evaluated IGFBP-3 mRNA expression and protein stability.
  • Investigated effects in a xenograft mouse model.

Main Results:

  • Akt activation significantly decreased IGFBP-3 mRNA expression and protein stability.
  • Akt suppression led to increased IGFBP-3 mRNA levels and protein stability.
  • Akt3 was identified as the primary mediator of Akt-induced IGFBP-3 regulation.
  • Overactivation of Akt3 correlated with suppressed IGFBP-3, while its inhibition enhanced IGFBP-3's antitumor effects.

Conclusions:

  • Akt3 functions as a negative regulator of IGFBP-3 in NSCLC.
  • Targeting Akt3 can enhance the antitumor efficacy of IGFBP-3.
  • Combined inhibition of IGFBP-3 and Akt3 presents a potential therapeutic strategy for NSCLC patients, particularly those with Akt3 overactivation.

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