4-Nonylphenol mediated tumor progression and immune modulation through CDK2: Computational and experimental...

Area of Science:

• Environmental Toxicology
• Cancer Biology
• Computational Chemistry

Background:

• 4-nonylphenol (4-NP) is an endocrine-disrupting chemical found in water systems globally.
• Elevated 4-NP levels are linked to cancer progression.
• Understanding 4-NP's carcinogenic mechanisms is crucial for public health.

Purpose of the Study:

• To systematically investigate the carcinogenic mechanisms of 4-NP.
• To identify oncogenic targets and prognostic markers associated with 4-NP exposure.
• To establish a computational-experimental framework for environmental toxicant assessment.

Main Methods:

• Network toxicology
• Machine learning
• Molecular docking simulations
• Single-cell RNA sequencing
• Spatial transcriptomics
• Pan-cancer expression profiling
• Breast cancer cell line experiments

Main Results:

• Identified six high-affinity 4-NP-binding targets: TNF, CDK2, PRKCA, ERBB2, CASP8, and MAPK3.
• Elucidated mechanisms involving MAPK signaling pathway activation and CD8+ T-cell exhaustion.
• Validated 4-NP's role in promoting cell proliferation and CDK2 expression in breast cancer cells.

Conclusions:

• 4-NP acts as a potential carcinogen by disrupting cellular signaling and immune surveillance.
• The study provides a novel computational-experimental framework for evaluating environmental toxicants.
• Findings offer insights for preventive strategies against pollutant-driven cancers.