TSPAN1: A Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance.

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A proteomic study revealed tetraspanin-1 (TSPAN1) as a protein involved in acquisition of cisplatin (CDDP) resistance (Data are available via ProteomeXchange with identifier PXD020159). TSPAN1 was found to increase in CDDP-resistant cells, CSCs and biopsies from head and neck squamous cell carcinoma (HNSCC) patients. TSPAN1 depletion in parental and CDDP-resistant HNSCC cells reduced cell proliferation, induced apoptosis, decreased autophagy, sensitized to chemotherapeutic agents and inhibited several signaling cascades, with phospho-SRC inhibition being a major common target. Moreover, TSPAN1 depletion in vivo decreased the size and proliferation of parental and CDDP-resistant tumors and reduced metastatic spreading. Notably, CDDP-resistant tumors showed epithelial-mesenchymal transition (EMT) features that disappeared upon TSPAN1 inhibition, suggesting a link of TSPAN1 with EMT and metastasis. Immunohistochemical analysis of HNSCC specimens further revealed that TSPAN1 expression was correlated with phospho-SRC (pSRC), and inversely with E-cadherin, thus reinforcing TSPAN1 association with EMT. Overall, TSPAN1 emerges as a novel oncogenic protein and a promising target for HNSCC therapy.", "claims": [{"id": "claim-method", "statement": "In first instance, One-way ANOVA and Post-Hoc analysis was applied to all cell groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33167355", "locator": "sections[18] \"2.16. 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Moreover, TSPAN1 depletion in vivo decreased the size and proliferation of pare", "S Spectrum (Perkin Elmer, Waltham, MA, USA). Mice were sacrificed by cervical dislocation. An autopsy was perf", "e Sciences, Corning, NY, USA). A total of 16 mice were included in the study, four mice for each of", "S Spectrum (Perkin Elmer, Waltham, MA, USA). Mice were sacrificed by cervical dislocation. An autop"], "order_basis": "paper_text_order:767", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ng a link of TSPAN1 with EMT and metastasis. Immunohistochemical analysis of HNSCC specimens further revealed", "etrospectively collected in order to perform immunohistochemistry (IHC) studies. All experimental procedures w", "ed in order to perform immunohistochemistry (IHC) studies. All experimental procedures were c", "further and significantly extend these data, immunohistochemical analysis of TSPAN1 were performed in a cohor"], "order_basis": "paper_text_order:1065", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["se and GFP as previously described [24], and transfected with siTSPAN1 vs. negative control (NC). For", "egative control (NC). 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