Related Experiment Video

Updated: May 22, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Neddylation as a target in PIK3CA-mutated head and neck cancer

Shorook Naara1, Zhibin Cui1, Adila Izgutdina1

  • 1Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.

Biochemical and Biophysical Research Communications
|March 28, 2025
PubMed

Insights

This study identified novel therapeutic targets in head and neck squamous cell carcinoma (HNSCC) with PIK3CA mutations. Neddylation pathway genes are essential in PIK3CA-mutated HNSCC, suggesting neddylation inhibitors as a potential therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phosphoinositide 3-kinase (PI3K) catalytic subunit alpha (PIK3CA) is frequently mutated in head and neck squamous cell carcinoma (HNSCC).
  • Identifying therapeutic vulnerabilities in PIK3CA-mutated HNSCC is crucial for developing targeted treatments.

Purpose of the Study:

  • To uncover genetic dependencies and potential therapeutic targets in PIK3CA-mutated HNSCC.
  • To investigate the role of the neddylation pathway in PIK3CA-mutated HNSCC.

Main Methods:

  • Utilized CRISPR interference (CRISPRi)-based genome-wide screening.
  • Conducted screening in an HPV-positive HNSCC cell line (UM-SCC-47) with a PIK3CA E545K mutation.
  • Performed validation experiments on identified key genes.

Main Results:

  • Identified 34 genes co-dependent with PIK3CA E545K mutation.
  • Discovered the essential role of 5 neddylation pathway genes, including NEDD8, NEDD8-MDP-1, and NAE1.
  • Confirmed a novel regulatory mechanism involving neddylation in PIK3CA-mutated HNSCC.

Conclusions:

  • PIK3CA mutation status may predict response to neddylation inhibitor therapy in HNSCC.
  • The neddylation pathway represents a promising therapeutic target for a subset of HNSCC patients.
  • Novel therapeutic strategies targeting the neddylation pathway can be explored for PIK3CA-mutated HNSCC.
Keywords:
CRISPR screenHead and neck cancerNeddylationPIK3CA mutation

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