Evidence map›Paper›PMID 40154000›Full record

ArticleBiochemical and biophysical research communications2025

Neddylation as a target in PIK3CA-mutated head and neck cancer.

Shorook Naara, Zhibin Cui, Adila Izgutdina, Nathan K VanLandingham, Andrew Nazarenko, Liam C Woerner, Becky Xu Hua Fu, Luke A Gilbert, Daniel E Johnson, Jennifer R Grandis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical and biophysical research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Shorook NaaraDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Zhibin CuiDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Adila IzgutdinaDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Nathan K VanLandinghamDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Andrew NazarenkoDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Liam C WoernerDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Becky Xu Hua FuArc Institute, 3181 Porter Drive, Palo Alto, CA, 94304, USA.
Luke A GilbertArc Institute, 3181 Porter Drive, Palo Alto, CA, 94304, USA; University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, 13 CA, San Francisco, USA; Department of Urology, University of California San Francisco, San Francisco, CA, USA; Innovative Genomics Institute, University of California-Berkeley, Berkeley, CA, USA.
Daniel E JohnsonDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA.
Jennifer R GrandisDepartment of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA. Electronic address: jennifer.grandis@ucsf.edu.

Funding

Integrating genomics and the protein interactome for HPV+ head and neck cancer therapyR35CA231998 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2018 to 2024
$6.2M
PI3K Pathway Mutations in Head and Neck CancerR01DE023685 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRANDIS, JENNIFER RUBIN, JOHNSON, DANIEL E · 2014 to 2023
$5.1M
NCI NIH HHS R35 CA231998NIDCR NIH HHS R01 DE023685
6 · The paper itself

Abstract

PIK3CA encodes the catalytic subunit of phosphoinositide 3-kinase (PI3K) enzyme and is the most commonly mutated oncogene in head and neck squamous cell carcinoma (HNSCC). This study aimed to identify potential therapeutic targets in HNSCC harboring mutant PIK3CA. We used CRISPR interference (CRISPRi)-based genome-wide screening methodology to reveal targetable genetic dependencies in PIK3CA-mutated HNSCC. Screening was conducted in an HPV-positive HNSCC cell line, UM-SCC-47, engineered to express the canonical E545K PIK3CA mutant. We identified 34 genes co-dependent on PIK3CA E545K mutation, including 5 genes in the neddylation pathway (NEDD8, NEDD8-MDP-1 and NAE1, USP8, UBA3). Validation experiments confirmed the essential role of NEDD8, NEDD8-MDP-1, and NAE1, indicating a novel regulatory mechanism in PIK3CA E545K-mutated HNSCC. Our findings suggest that PIK3CA mutation may serve as a predictive biomarker for neddylation inhibitor therapy in a subpopulation of HNSCC.

Indexed as

Class I Phosphatidylinositol 3-KinasesHead and Neck NeoplasmsNEDD8 ProteinCell Line, TumorHumansMutationSquamous Cell Carcinoma of Head and NeckUbiquitin-Activating EnzymesClass I Phosphatidylinositol 3-KinasesNAE protein, humanNEDD8 ProteinNEDD8 protein, humanPIK3CA protein, humanUbiquitin-Activating EnzymesCRISPR screenHead and neck cancerNeddylationPIK3CA mutation

Identifiers

PMID40154000
PMCPMC12036330

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.