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Updated: Sep 19, 2025

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PLK4 is a potential therapeutic target in nonmelanoma skin cancers: Evidence from molecular and in vivo studies

Mary A Ndiaye1, Debra R Garvey1, Gagan Chhabra1

  • 1Department of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Photochemistry and Photobiology
|June 17, 2025
PubMed

Insights

Polo-like kinase 4 (PLK4) is overexpressed in nonmelanoma skin cancers (NMSC). Inhibiting PLK4 reduced cancer cell growth and tumor formation, suggesting PLK4 as a potential therapeutic target for skin cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Nonmelanoma skin cancers (NMSC), including cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC), are the most common cancers in the US, linked to UV radiation.
  • Current treatments for advanced NMSC are limited, necessitating novel targeted therapies to improve outcomes and overcome resistance.
  • The role of Polo-like kinase 4 (PLK4) in NMSC pathogenesis and its potential as a therapeutic target remain largely unestablished.

Purpose of the Study:

  • To investigate the role of Polo-like kinase 4 (PLK4) in nonmelanoma skin cancers (NMSC).
  • To evaluate the therapeutic potential of inhibiting PLK4 in cutaneous squamous cell carcinoma (cSCC) and basal cell carcinoma (BCC) models.

Main Methods:

  • PLK4 expression levels were assessed in NMSC cell lines and tissues.
  • The effects of PLK4 inhibition using small molecule inhibitors (centrinone, CFI-400945) and CRISPR/Cas9-mediated knockdown were evaluated in vitro and in vivo.
  • Cell viability, proliferation, apoptosis, cell cycle progression, and gene expression were analyzed.

Main Results:

  • PLK4 was found to be significantly overexpressed in BCC and cSCC cells and tissues.
  • Inhibition of PLK4 decreased cell viability, proliferation, and clonogenic survival in human cSCC and BCC cells.
  • PLK4 inhibition induced cell cycle arrest, apoptosis, and modulated key cancer-related genes, with significant growth inhibition in vitro and reduced tumorigenesis in vivo.

Conclusions:

  • PLK4 is significantly overexpressed in nonmelanoma skin cancers (NMSC) and plays a crucial role in cancer cell proliferation and survival.
  • Targeting PLK4 with small molecule inhibitors or genetic knockdown demonstrates significant anti-cancer effects in NMSC models.
  • PLK4 represents a promising therapeutic target and potential biomarker for the management of NMSC.
Keywords:
CFI‐400945PLK4centrinonepolo‐like kinase

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