ArticleNeoplasia (New York, N.Y.)2025
XAF1 is secreted from stressed tumor cells to activate T cell-mediated tumor surveillance via Lck-ERK signaling.
Article in Neoplasia (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A novel ubiquitin-related genes-based signature demonstrated values in prognostic prediction, immune landscape sculpture and therapeutic options in laryngeal cancer.Frontiers in pharmacology · 2025Article
- Application of Cord Blood-Derived Exosomes in Tumor Prevention and Treatment.Clinical Medicine Insights. Oncology · 2025Review
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Authors and funding
6 authors.
Funding
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Abstract
X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in multiple types of human malignancies. Nevertheless, the molecular basis for the XAF1-mediated tumor suppression remains largely undefined. Here, we report that XAF1 is secreted from cells under various cytotoxic stress conditions and activates T cell-mediated tumor surveillance. In cancer cells exposed to interferon -γ, tumor necrosis factor -α, and etoposide, XAF1 is elevated and actively secreted through the unconventional endo-lysosomal trafficking pathway and the zinc finger 4 domain of XAF1 plays an essential for this secretion. Secreted XAF1 is internalized into nearby T cells through clathrin-mediated endocytosis and stimulates proliferation, migration, and tumor infiltration of T cells. Internalized XAF1 activates RAF-MEK-ERK signaling through the direct interaction with and phosphorylation of lymphocyte-specific protein tyrosine kinase. In response to interferon -γ injection, Xaf1
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