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Updated: May 9, 2025

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HIPK4 accelerates cutaneous squamous cell carcinoma progression by phosphorylating TAp63 and inhibiting EFEMP1

Ze Guo1, Bingjie Chen1, Mengya Zhang1

  • 1Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, P.R. China.

The Journal of Biological Chemistry
|May 2, 2025
PubMed

Insights

Homeodomain interacting protein kinase 4 (HIPK4) drives cutaneous squamous cell carcinoma (CSCC) progression by inhibiting EFEMP1 via TAp63 phosphorylation. Targeting HIPK4 may offer a new therapeutic strategy for CSCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer with metastatic potential.
  • Homeodomain interacting protein kinase 4 (HIPK4) inhibits skin epithelial differentiation, but its role in CSCC is unknown.
  • HIPK4 is upregulated in CSCC tissues, suggesting a role in tumorigenesis.

Purpose of the Study:

  • To investigate the role of HIPK4 in CSCC progression.
  • To elucidate the molecular mechanisms by which HIPK4 regulates CSCC.
  • To evaluate HIPK4 as a potential therapeutic target for CSCC.

Main Methods:

  • Co-immunoprecipitation (Co-IP) and GST-pull down assays to analyze protein interactions.
  • Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays to study gene regulation.
  • In vitro assays for cell proliferation, migration, and invasion; in vivo tumor growth studies in mice.

Main Results:

  • EFEMP1 expression is decreased in CSCC; its overexpression suppresses CSCC cell malignancy.
  • HIPK4 is upregulated in CSCC and its knockdown inhibits tumor growth and malignant behaviors.
  • HIPK4 phosphorylates TAp63, decreasing EFEMP1 expression and promoting CSCC progression.

Conclusions:

  • HIPK4 promotes CSCC progression by inhibiting EFEMP1 through TAp63 phosphorylation.
  • HIPK4 is a potential therapeutic target for cutaneous squamous cell carcinoma.
  • This study provides insights into CSCC molecular mechanisms and therapeutic strategies.
Keywords:
EFEMP1HIPK4TAp63cutaneous squamous cell carcinomaphoshorylation

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