{"doi":"10.1016/j.bbrc.2025.152976","title":"Taming Bacterial Toxins into an Anticancer Platform","abstract":"A hallmark of cancer is uncontrolled cell growth, which leads to hypoxia. Hypoxia causes significantly increased expression of a carbohydrate antigen Sialyl Lewis X (SLeX). The expression of SLeX correlates with recurrence, poor prognosis, and a low survival rate in a broad spectrum of cancers. Treatment targeting SLeX inhibits cancer cell migration and stimulates cell death, bringing a new chapter to cancer therapy. Our previous study shows that SSL11 (staphylococcal superantigen-like protein 11) mediates cell motility arrest by inducing adhesion via binding to SLeX. The properties of binding glycan SLeX and inhibiting the cell motility of SSL11 make it an appealing delivery platform against cancers that overexpress SLeX. Pseudomonas exotoxin A (PE) is an ADP-ribosylating AB toxin used to construct immunotoxins by replacing the receptor-binding domain with antibodies. A truncated and mutated form of PE (PE24 M10 ) was used in immunotoxins with promising results against multiple cancers. In this study, we successfully constructed and purified SSL11-PE24 M10 . For proof of principle, we tested the anticancer activities of SSL11-PE24 M10 in human cancer cells. We found that SSL11-PE24 M10 , not PE24 M10 , entered cells, induced cell death, and inhibited cell migration in multiple cancer cell lines in a dose-dependent manner. SSL11-PE24 M10 displays lower toxicity in normal human lung epithelial cells and elicits low immunogenicity in mice. Therefore, our study will provide new ideas for our battle against cancer, especially those prone to metastasis. • We developed an anticancer platform targeting a cancer marker induced by hypoxia. • SSL11-PE24 M10 induced cell death in multiple cancer cell lines dose-dependently. • SSL11-PE24 M10 inhibited cancer cell migration in a dose- and time-dependent manner. • SSL11-PE24 M10 displays lower toxicity in normal human lung epithelial cells. • SSL11-PE24 M10 is a potential anticancer platform with low off-target activities and low immunogenicity in mice.","journal":"Biochemical and Biophysical Research Communications","year":2025,"id":582725,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1494714,"name":"Chen Chen","orcid":"0000-0003-3974-2952","position":1,"is_corresponding":false},{"id":1494713,"name":"Chen Yang","orcid":"0000-0002-7934-9269","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":"41259960","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}