AXL and MET Crosstalk in Canine Mammary Tumors: A Combined Interactome and Gene Ontology Analysis

Background: Canine mammary tumors (CMTs) resemble human breast cancer in molecular and clinical aspects, including hormonal influences and oncogenic RTKs like AXL and MET. CMTs serve as a model for cross-species tumor biology. This study investigates the shared AXL-MET interactome and pathways to uncover targets for dual RTK inhibition. Methods: AXL and MET Protein-Protein interactions (PPI) networks were sourced from BioGRID, supplemented by human breast cancer data due to CMT data scarcity and high conservation. Overlaps were identified via Venn analysis. The integrated interactome was constructed in STRING and visualized in Cytoscape, with hubs assessed by degree, betweenness, and connectivity. Gene Ontology enrichment for biological processes, molecular functions, and cellular components was performed on ۱۱ genes using RStudio. Results: EGFR and MET emerged as key hubs with high connectivity (Degree: ۱۰; Closeness: ۱.۰; Betweenness: ۰.۱۳۵), orchestrating tumor growth pathways. AXL, CBL, and GAB۱ showed moderate links (Degree: ۷–۹), while STUB۱, SHC۲/۴, and CBL-related proteins were peripheral (Degree: ۴–۵). The network was highly clustered (Coefficient: ۰.۵۸–۱.۰) and radial (≥۰.۹۴). GO analysis revealed enrichments in ERBB signaling, kinase activity, and membrane processes promoting proliferation and invasion (Gene Ratio: ۰.۳۵–۰.۵۰; adj. p: ۰.۰۱–۰.۰۴). Conclusion: EGFR and MET are pivotal in CMT signaling, aided by modulators like AXL and CBL, and peripherals like STUB۱.

کلیدواژه ها:

Breast cancer ، PPI ، Receptor tyrosine kinase ، String ، Interactome