Functional profiling of the chaperone systems interactome in breast cancer using experimental and machine-learning...

Area of Science:

• Molecular Biology
• Cancer Research
• Proteostasis

Background:

• Breast cancer heterogeneity arises from molecular changes, including proteostasis loss.
• Chaperone system dysfunction contributes to proteostasis loss, but its role in breast cancer is not fully understood.

Purpose of the Study:

• To characterize chaperone expression and client protein interactions in breast cancer.
• To elucidate the role of chaperone dysregulation in shaping tumor biology and identify potential therapeutic targets.

Main Methods:

• Identified 53 chaperones in breast tissue, with 26 differentially expressed in tumors.
• Constructed protein-protein interaction (PPI) networks for major chaperone families using interaction data, machine learning, and molecular docking.
• Performed pathway enrichment analyses on PPI networks.

Main Results:

• Each chaperone family's PPI network showed distinct client proteins and pathway enrichment.
• HSP70 network linked to DNA repair and immunomodulation (interleukin, cytokine signaling).
• HSP90 network associated with MAPK, PI3K/AKT/mTOR signaling, EMT, and cell cycle control.
• CCT/TRiC chaperonins implicated in cytoskeleton dynamics, mitosis, and autophagy.

Conclusions:

• Chaperone dysregulation significantly influences breast cancer biology.
• Identified novel chaperone client proteins and pathways involved in tumorigenesis.
• Chaperones represent promising therapeutic targets for breast cancer treatment.