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Updated: Apr 18, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

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The T-box transcription factor, TBX3, is a key substrate of AKT3 in melanomagenesis

Jade Peres1, Shaheen Mowla1, Sharon Prince1

  • 1Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925, Cape Town, South Africa.

Oncotarget
|January 18, 2015
PubMed

Insights

The AKT3 pathway impacts melanoma by regulating the TBX3 transcription factor. Phosphorylation of TBX3 by AKT3 enhances melanoma cell invasion and E-cadherin repression, revealing a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The AKT3 signaling pathway is crucial in melanoma development and metastasis.
  • The transcription factor TBX3 is upregulated in some melanomas, promoting invasion by repressing E-cadherin.

Purpose of the Study:

  • To investigate the functional link between AKT3 and TBX3 in melanoma.
  • To identify the molecular mechanisms by which TBX3 contributes to melanoma progression.

Main Methods:

  • Site-directed mutagenesis and in vitro kinase assays to identify AKT3 phosphorylation sites on TBX3.
  • Western blotting, immunofluorescence, and reporter assays to assess protein stability, localization, and transcriptional activity.
  • Migration and invasion assays to evaluate functional consequences.

Main Results:

  • Identified serine 720 (S720) as the key AKT3 phosphorylation site on TBX3.
  • Demonstrated that AKT3-mediated phosphorylation of TBX3 at S720 enhances its stability and nuclear localization.
  • Showed that phosphorylated TBX3 represses E-cadherin transcription, promoting melanoma cell migration and invasion.

Conclusions:

  • Established a novel signaling network linking AKT3, TBX3, and E-cadherin in melanoma.
  • TBX3 phosphorylation by AKT3 is a critical driver of melanoma cell migration and invasion.
  • TBX3 represents a potential therapeutic target for anti-metastatic melanoma treatments.

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