RESUMEN
Ephrin receptor A2 (EphA2), a member of the Ephrin receptor family, is closely related to the progression of oral squamous cell carcinoma (OSCC). Cancer stem cells (CSCs) play essential roles in OSCC development and occurrence. The underlying mechanisms between EphA2 and CSCs, however, are not yet fully understood. Here, we found that EphA2 was overexpressed in OSCC tissues and was associated with poor prognosis. Knockdown of EphA2 dampened the CSC phenotype and the tumour-initiating frequency of OSCC cells. Crucially, the effects of EphA2 on the CSC phenotype relied on KLF4, a key transcription factor for CSCs. Mechanistically, EphA2 activated the ERK signalling pathway, promoting the nuclear translocation of YAP. Subsequently, YAP was bound to TEAD3, leading to the transcription of KLF4. Overall, our findings revealed that EphA2 can enhance the stemness of OSCC cells, and this study identified the EphA2/KLF4 axis as a potential target for treating OSCC.
Asunto(s)
Carcinoma de Células Escamosas , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel , Neoplasias de la Boca , Células Madre Neoplásicas , Receptor EphA2 , Factor 4 Similar a Kruppel/metabolismo , Humanos , Receptor EphA2/metabolismo , Receptor EphA2/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Animales , Ratones , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Femenino , Ratones Desnudos , Masculino , Pronóstico , Sistema de Señalización de MAP Quinasas/genética , Transcripción GenéticaRESUMEN
Targeting metabolic reprogramming may be an effective strategy to enhance cancer treatment efficacy. Glutamine serves as a vital nutrient for cancer cells. Inhibiting glutamine metabolism has shown promise in preventing tumor growth both in vivo and in vitro through various mechanisms. Therefore, this review collates recent scientific literature concerning the correlation between glutamine metabolism and cancer treatment. Novel treatment modalities based on amino acid transporters, metabolites, and glutaminase are discussed. Moreover, we demonstrate the relationship between glutamine metabolism and tumor proliferation, drug resistance, and the tumor immune microenvironment, offering new perspectives for the clinical treatment of head and neck squamous cell carcinoma, particularly for combined therapies. Identifying innovative approaches for enhancing the efficacy of glutamine-based metabolic therapy is crucial to improving HNSCC treatment.
Asunto(s)
Glutamina , Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Glutamina/metabolismo , Humanos , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Animales , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Microambiente Tumoral/efectos de los fármacos , Glutaminasa/metabolismo , Glutaminasa/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Molecular DirigidaRESUMEN
OBJECTIVE: To identify the factors that affect the implementation of workers' manuals of occupational health and safety management system (OHSMS). METHODS: A self-designed questionnaire, which contained 23 items, was used to investigate workers' knowledge, responsibility and supporting environment of the OHSMS. The Logistic Regression Model was developed to identify factors that affect the implementation of the OHSMS. RESULTS: Demographic characteristics did not affect the implementation of the OHSMS manual. Knowledge (six out of seven items), responsibility and supporting environment had significant impact on the implementation of the OHSMS manuals. CONCLUSION: A variety of factors affect workers' compliance to the OHSMS manuals and need to be better controlled.
