SDCBP modulates stemness and chemoresistance in head and neck squamous cell carcinoma through src activation
Mir Pérez, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Garcia Mayea, Yoelsis (Hospital Universitari Vall d'Hebron. Institut de Recerca)
García Fernández, Laia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Herrero, Pol (Universitat Rovira i Virgili)
Canela, Núria (Universitat Rovira i Virgili)
Tabernero, Rocío (Hospital Universitari Vall d'Hebron)
Lorente Guerrero, Juan (Hospital Universitari Vall d'Hebron)
Castellvi, Josep (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Allonca, Eva (Universidad de Oviedo)
García-Pedrero, Juana (Universidad de Oviedo)
Rodrigo, Juan Pablo (Universidad de Oviedo)
Carracedo, Ángel (Complejo Hospitalario Universitario de Santiago de Compostela)
LLeonart, Matilde Esther (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Date:	2021
Abstract:	To characterize the mechanisms that govern chemoresistance, we performed a comparative proteomic study analyzing head and neck squamous cell carcinoma (HNSCC) cells: CCL-138 (parental), CCL-138-R (cisplatin-resistant), and cancer stem cells (CSCs). Syntenin-1 (SDCBP) was upregulated in CCL-138-R cells and CSCs over parental cells. SDCBP depletion sensitized biopsy-derived and established HNSCC cell lines to cisplatin (CDDP) and reduced CSC markers, Src activation being the main SDCBP downstream target. In mice, SDCBP-depleted cells formed tumors with decreased mitosis, Ki-67 positivity, and metastasis over controls. Moreover, the fusocellular pattern of CCL-138-R cell-derived tumors reverted to a more epithelial morphology upon SDCBP silencing. Importantly, SDCBP expression was associated with Src activation, poor differentiated tumor grade, advanced tumor stage, and shorter survival rates in a series of 382 HNSCC patients. Our results reveal that SDCBP might be a promising therapeutic target for effectively eliminating CSCs and CDDP resistance.
Grants:	Instituto de Salud Carlos III CP03/00101 Instituto de Salud Carlos III IDI2018/155 Ministerio de Economía y Competitividad PI15/01262 Instituto de Salud Carlos III PI19/00560
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Cancers, Vol. 13 Núm. 19 (10-1 2021) , p. 4952, ISSN 2072-6694

DOI: 10.3390/cancers13194952
PMID: 34638436

18 p, 6.2 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles