TSPAN1 : a Novel Protein Involved in Head and Neck Squamous Cell Carcinoma Chemoresistance
Garcia Mayea, Yoelsis (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Mir Pérez, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Carballo, Laia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castellvi, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Temprana-Salvador, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lorente, Juan (Hospital Universitari Vall d'Hebron)
Benavente, Sergi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García-Pedrero, Juana María (Centro de Investigación Biomédica en Red de Cáncer)
Allonca, Eva (Centro de Investigación Biomédica en Red de Cáncer)
Rodrigo, Juan Pablo (Centro de Investigación Biomédica en Red de Cáncer)
LLeonart, Matilde E. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

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

DOI: 10.3390/cancers12113269
PMID: 33167355

20 p, 4.5 MB

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