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Página principal > Artículos > Artículos publicados > TSPAN1 : |
Fecha: | 2020 |
Resumen: | Sensitization of resistant cells and cancer stem cells (CSCs) represents a major challenge in cancer therapy. 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. |
Ayudas: | Instituto de Salud Carlos III PI15-01262 Instituto de Salud Carlos III PI19-00560 Instituto de Salud Carlos III CP03-00101 Instituto de Salud Carlos III CB16/12-00390 |
Nota: | Altres ajuts: This work was supported by grants from the Instituto de Salud Carlos III, Ayudas a Grupos PCTI Principado de Asturias (IDI2018/155 to J.P.R.), co-financed by the European Regional Fund (ERDF) and AECC (Spanish Association of Cancer Research) Founding Ref. GC16173720CARR (M.E.L.). Y.G.-M. and C.M. were granted by the VHIR and iP-FIS (ISCIII) fellowships respectively. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Cancer ; HNSCC ; Resistance ; Cancer stem cells ; Apoptosis ; Autophagy |
Publicado en: | Cancers, Vol. 12 Núm. 11 (2020) , p. 3269, ISSN 2072-6694 |
20 p, 4.5 MB |