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A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
07:41

A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis

Published on: March 8, 2022

Regulation of gene expression in melanoma: new approaches for treatment

Michael C Leslie1, Menashe Bar-Eli

  • 1Department of Cancer Biology, MD Anderson Cancer Center, Houston, Texas 77230-1429, USA.

Journal of Cellular Biochemistry
|November 4, 2004
PubMed

Insights

Melanoma progression involves losing AP-2, leading to increased MCAM/MUC18 and IL-8. Targeting transcription factors CREB/ATF-1 inhibits melanoma metastasis and tumorigenicity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Melanoma progression from radial growth phase (RGP) to metastatic vertical growth phase (VGP) involves poorly understood molecular changes.
  • Transcription factor AP-2 loss is linked to melanoma progression.

Purpose of the Study:

  • To elucidate molecular alterations during melanoma RGP to VGP transition.
  • To investigate the role of AP-2, CREB, and ATF-1 in melanoma progression.
  • To explore novel therapeutic targets and antibodies for melanoma treatment.

Main Methods:

  • Analysis of gene expression changes in melanoma cells during progression.
  • Functional studies using dominant-negative CREB and anti-ATF-1 single chain antibody fragments (ScFv).
  • In vivo studies assessing tumorigenicity and metastatic potential.
  • Development of fully human antibodies against MCAM/MUC18 and IL-8.

Main Results:

  • Loss of AP-2 in metastatic melanoma correlates with overexpression of MCAM/MUC18, MMP-2, PAR-1, and IL-8, and reduced c-KIT.
  • Overexpression of transcription factors CREB and ATF-1 is associated with melanoma progression.
  • Inactivation of CREB/ATF-1 reduces MMP-2 and MCAM/MUC18, increases apoptosis sensitivity, and inhibits in vivo tumorigenicity and metastasis.
  • Development of anti-MCAM/MUC18 and anti-IL-8 antibodies.

Conclusions:

  • AP-2 and CREB/ATF-1 play critical roles in human melanoma progression and metastasis.
  • Targeting CREB/ATF-1 pathways offers a potential strategy to inhibit melanoma growth and spread.
  • Anti-MCAM/MUC18 and anti-IL-8 antibodies represent promising new therapeutic modalities for melanoma treatment.

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