Vesicle trafficking 1 in breast cancer tissue and serum orchestrates metastatic progression and an immunosuppressive microenvironment.

Breast cancer remains the leading cause of cancer-related mortality among women, primarily due to recurrence and metastasis. Although the tumor microenvironment contributes to metastasis and invasion, the underlying mechanisms remain incompletely understood. Vesicle trafficking 1 (VTA1) is implicated in multiple cellular functions, but its specific role and clinical significance in breast cancer remain unclear. This study aimed to evaluate the expression, biological function, and clinical relevance of VTA1 in breast cancer, together with its impact on the tumor microenvironment. VTA1 was significantly upregulated at the mRNA, protein and serum levels in breast cancer. High VTA1 expression in both cancer and stromal cells correlated with advanced clinical stage, distant metastasis and poor overall survival, serving as an independent prognostic factor. Functionally, VTA1 acted as a pro-metastatic driver in breast cancer, specifically enhancing the migratory and invasive capacities of cancer cells without affecting proliferation. Moreover, VTA1 expression was positively associated with an immunosuppressive microenvironment, including M2 macrophage infiltration in both tumor and stromal regions, as well as stromal cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) expression. Mechanistically, VTA1-interacting proteins were enriched in metastasis and immunosuppression-linked pathways, such as tight junction and endocytosis. In conclusion, this study identifies VTA1 as a pro-metastatic driver that promotes metastasis and fosters an immunosuppressive microenvironment in breast cancer. Serum VTA1 may serve as a non-invasive diagnostic biomarker, while tissue VTA1 expression independently predicts poor prognosis.