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Fibulin-3 Has Anti-Tumorigenic Activities in Cutaneous Squamous Cell Carcinoma

Xin Wang1, Qing Zhang2, Changji Li3

  • 1Department of Dermatology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

The Journal of Investigative Dermatology
|February 10, 2019
PubMed

Insights

Fibulin-3, a protein, is downregulated in cutaneous squamous cell carcinoma (cSCC). Restoring fibulin-3 inhibits cSCC growth, proliferation, and metastasis, suggesting it

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer globally.
  • Fibulin-3's role in cSCC tumorigenesis has not been previously elucidated.
  • Altered gene expression and epigenetic modifications, like promoter methylation, are implicated in cancer development.

Purpose of the Study:

  • To investigate the expression status and functional role of fibulin-3 in cutaneous squamous cell carcinoma.
  • To determine the underlying mechanism of fibulin-3 downregulation in cSCC.
  • To evaluate fibulin-3's potential as a therapeutic target for cSCC.

Main Methods:

  • Quantitative analysis of fibulin-3 expression in cSCC tissues versus normal skin.
  • Assessment of fibulin-3 promoter methylation status.
  • In vitro studies using cSCC cell lines (A431, SCL-1) with fibulin-3 knockdown and overexpression.
  • Cellular assays measuring proliferation, apoptosis, migration, and invasion.
  • Western blot analysis to assess the AKT signaling pathway.
  • In vivo mouse xenograft model to evaluate tumor growth inhibition.

Main Results:

  • Fibulin-3 expression was significantly downregulated in cSCC tissues, correlated with promoter methylation.
  • Fibulin-3 knockdown promoted cSCC cell proliferation, survival, migration, and invasion.
  • Fibulin-3 overexpression inhibited proliferation, induced G1/S phase arrest, promoted apoptosis, and reduced migration/invasion.
  • Fibulin-3's anti-tumorigenic effects were linked to the inhibition of the AKT signaling pathway.
  • Overexpression of fibulin-3 suppressed cSCC tumor growth in vivo.

Conclusions:

  • Fibulin-3 exhibits significant anti-tumorigenic properties in cutaneous squamous cell carcinoma.
  • Downregulation of fibulin-3, driven by promoter methylation, contributes to cSCC progression.
  • Fibulin-3 represents a promising novel therapeutic target for cSCC treatment.

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