1. SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation
- Author
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Laia Garcia, Pol Herrero, Juan P. Rodrigo, Núria Canela, Rocío Tabernero, Cristina Mir, Juan Lorente, Juana M. García-Pedrero, Eva Allonca, Yoelsis Garcia-Mayea, Josep Castellví, Matilde E. Lleonart, Angel Carracedo, Institut Català de la Salut, [Mir C] Grup de Recerca Biomèdica en Cèl•lules Mare del Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Faculty of Medicine, University of Barcelona, Barcelona, Spain. [Garcia-Mayea Y, Garcia L, Castellvi J] Grup de Recerca Biomèdica en Cèl•lules Mare del Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Herrero P, Canela N] Eurecat, Centre Tecnològic de Catalunya–Centre for Omic Sciences (COS), Joint Unit Universitat Rovira i Virgili-EURECAT, Reus, Spain. [Tabernero R, Lorente J] Servei d’Otorinolaringologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [LLeonart ME] Grup de Recerca Biomèdica en Cèl•lules Mare del Càncer, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Spanish Biomedical Research Network Centre in Oncology, CIBERONC, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
cancer stem cells ,Cancer Research ,Physiological Phenomena::Pharmacological and Toxicological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasm [PHENOMENA AND PROCESSES] ,Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores] ,Biology ,Other subheadings::Other subheadings::/drug therapy [Other subheadings] ,HNSCC ,Article ,Metastasis ,stemness ,Downregulation and upregulation ,Coll - Càncer - Tractament ,Cancer stem cell ,Neoplasms::Neoplasms by Site::Head and Neck Neoplasms [DISEASES] ,medicine ,Gene silencing ,Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma, Squamous Cell [DISEASES] ,neoplasias::neoplasias por localización::neoplasias de cabeza y cuello [ENFERMEDADES] ,neoplasias::neoplasias por tipo histológico::neoplasias glandulares y epiteliales::carcinoma::carcinoma de células escamosas [ENFERMEDADES] ,RC254-282 ,Resistència als medicaments ,Cisplatin ,fenómenos fisiológicos::fenómenos farmacológicos y toxicológicos::fenómenos farmacológicos::resistencia a medicamentos::resistencia a los antineoplásicos [FENÓMENOS Y PROCESOS] ,chemoresistance ,SDCBP ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Head and neck squamous-cell carcinoma ,Cap - Càncer - Tractament ,Oncology ,Cell culture ,Cancer research ,medicine.drug ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Simple Summary Drug resistance is the principal limiting factor to achieving good survival rates in patients with cancer. The identification of potential biomarkers for diagnosis and prognostic prediction, as well as the design of new molecular-targeted treatments, will be essential to improving head and neck squamous cell carcinoma (HNSCC) patient outcomes. In this sense, the sensitization of resistant cells and cancer stem cells (CSCs) represents a major challenge in cancer therapy. We conducted a proteomic study involving cisplatin-resistance and CSCs with the aim to unravel the molecular and cellular mechanisms by which tumor cells acquire resistance to chemotherapy. Syntenin-1 (SDCBP) was identified as an important protein involved in the chemoresistance and stemness of HNSCC tumors. 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.
- Published
- 2021