Abstract
Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is frequently upregulated in various cancers, including triple-negative breast cancer (TNBC), and is associated with poor clinical outcomes. Analysis of The Cancer Genome Atlas (TCGA) data confirmed that PTK7 mRNA expression is significantly higher in TNBC tumor tissues compared with adjacent normal tissues and non-TNBC breast cancer subtypes. Kaplan–Meier survival analysis demonstrated a strong correlation between high PTK7 expression and worse relapse-free survival in TNBC patients (HR = 1.46, p = 0.015). In vitro, anti-PTK7 monoclonal antibodies (mAbs) significantly reduced proliferation, wound healing, migration, and invasion in TNBC MDA-MB-231 cells. Ki-67 immunofluorescence assays revealed substantial decreases in cell proliferation following treatment with PTK7 mAbs (32-m, 43-m, 50-m, and 52-m). Moreover, actin polymerization, a critical process in cell migration and invasion, was markedly impaired upon PTK7 mAb treatment. In vivo, PTK7 mAbs significantly reduced tumor volume and weight in a TNBC xenograft mouse model compared with controls. Treated tumors exhibited decreased expression of Ki-67 and vimentin, indicating reduced proliferation and epithelial-to-mesenchymal transition. These findings highlight PTK7 as a promising therapeutic target in TNBC and demonstrate the potent anti-cancer effects of PTK7-neutralizing mAbs both in vitro and in vivo. Further exploration of PTK7-targeted therapies, including humanized mAbs and antibody-drug conjugates, is warranted to advance treatment strategies for PTK7-positive TNBC.
Published Version
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