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Early Growth Response-1 Suppresses Human Fibrosarcoma Cell Invasion and Angiogenesis

Ruochun Huang1, Shiyong Li2, Weimin Yang1

  • 1Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.

Cancer Genomics & Proteomics
|August 10, 2019
PubMed

Insights

Early Growth Response-1 (Egr-1) acts as a tumor suppressor by inhibiting cancer cell invasion and angiogenesis. Egr-1 up-regulates tissue inhibitor of metalloproteinase-2 (TIMP-2), which further suppresses tumor cell invasion and blood vessel formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor development involves genetic and epigenetic changes affecting gene expression controlled by transcription factors.
  • Early Growth Response-1 (Egr-1) is a transcription factor with potential tumor suppressor functions.
  • Investigating Egr-1's role in suppressing tumor invasion, angiogenesis, and metastasis is crucial.

Purpose of the Study:

  • To investigate the role of Egr-1 in suppressing tumor cell invasion, angiogenesis, and metastasis.
  • To explore the molecular mechanisms underlying Egr-1's tumor-suppressive functions.
  • To determine the involvement of tissue inhibitor of metalloproteinase-2 (TIMP-2) in Egr-1-mediated suppression.

Main Methods:

  • Egr-1 expression in human fibrosarcoma cells and mouse embryonic fibroblasts (MEFs) from Egr-1 knockout and wild-type mice.
  • Assessing cell invasion through matrigel and endothelial cell proliferation, invasion, and tube formation using conditioned media.
  • Utilizing human cytokine antibody arrays to examine gene expression and mouse skin plug assays for in vivo angiogenesis.
  • Evaluating the effect of TIMP-2 on fibrosarcoma cell invasion.

Main Results:

  • Egr-1 expression significantly reduced fibrosarcoma cell invasion and endothelial cell proliferation and invasion.
  • Egr-1 knockout MEFs exhibited increased invasion compared to wild-type MEFs.
  • Egr-1 transfection up-regulated tissue inhibitor of metalloproteinase-2 (TIMP-2) expression.
  • TIMP-2, along with Egr-1 conditioned medium, suppressed fibrosarcoma cell invasion and angiogenesis.

Conclusions:

  • Egr-1 demonstrates novel functions in suppressing tumor cell invasion and angiogenesis.
  • TIMP-2 plays a significant role in the tumor invasion and angiogenesis suppression mediated by Egr-1.
  • Egr-1 represents a potential therapeutic target for inhibiting cancer progression.
Keywords:
Egr-1TIMP-2angiogenesisfibrosarcomainvasionmetastasisprotein arrays

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