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Updated: Dec 23, 2025

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

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FBXO25 Promotes Cutaneous Squamous Cell Carcinoma Growth and Metastasis through Cyclin D1

Aleksandar Kuzmanov1, Pål Johansen1, Günther Hofbauer1

  • 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

The Journal of Investigative Dermatology
|April 27, 2020
PubMed

Insights

FBXO25 promotes cutaneous squamous cell carcinoma (cSCC) growth by interacting with Oct-1, which stabilizes cyclin D1. Silencing FBXO25 reduces tumor growth, highlighting FBXO25 as a potential therapeutic target for cSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • F-box proteins (FBPs) are key components of SCF E3 ubiquitin ligase complexes, regulating protein degradation and cellular processes.
  • FBPs bind substrates to control various tumor behaviors, but the specific role of FBXO25 in cutaneous squamous cell carcinoma (cSCC) remains uninvestigated.

Purpose of the Study:

  • To investigate the role of FBXO25 in the development and progression of cutaneous squamous cell carcinoma (cSCC).
  • To elucidate the molecular mechanisms by which FBXO25 influences cSCC growth and metastasis, particularly its relationship with cyclin D1 and Oct-1.

Main Methods:

  • Quantitative analysis of FBXO25 expression in cSCC tissues and cell lines compared to normal keratinocytes.
  • In vitro and in vivo experiments involving stable silencing and overexpression of FBXO25 and cyclin D1 in SCC13 cells.
  • Co-immunoprecipitation assays to determine the interaction between FBXO25, cyclin D1, and Oct-1.

Main Results:

  • FBXO25 is significantly upregulated in cSCC tissues and cell lines compared to normal keratinocytes.
  • FBXO25 knockdown in SCC13 cells reduced tumor growth and downregulated cyclin D1 expression.
  • Overexpression of cyclin D1 in FBXO25-deficient cells restored tumor growth, indicating FBXO25 promotes cSCC via cyclin D1.
  • Oct-1 directly interacts with FBXO25, and its downregulation leads to cyclin D1 stabilization, promoting tumor growth and metastasis.

Conclusions:

  • FBXO25 plays a crucial role in promoting cSCC growth and metastasis.
  • The mechanism involves FBXO25 interacting with Oct-1, leading to Oct-1 downregulation, subsequent cyclin D1 stabilization, and enhanced tumor progression.
  • Targeting FBXO25 or modulating the FBXO25-Oct-1-cyclin D1 axis presents a potential therapeutic strategy for cSCC.

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