RESUMEN
BACKGROUND: Lung squamous cell carcinoma (LUSC) is recognized as the major subtypes of non-small cell lung cancer (NSCLC). Circulating tumor cells (CTCs) are critical players in tumor metastasis. A molecular profiling of CTCs has previously identified notch receptor 1 (Notch1) as an important mediator in NSCLC. Therefore, we investigate Notch1 roles in LUSC and its related mechanisms. METHODS: The serum levels of Notch1 were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The CTCs isolated from blood samples were characterized via an immunofluorescence method. Cell motion was determined using Transwell chambers. The regulatory relationship between Notch1 and zinc finger E-box-binding homeobox 1 (ZEB1) was verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The protein levels were detected by western blotting. RESULTS: Higher Notch1 expression in patients with LUSC than that in normal controls was observed. Notch1 knockdown inhibited cell motion and epithelial-mesenchymal transition (EMT). ZEB1 transcriptionally activated Notch1. ZEB1 upregulation exacerbated the malignant phenotypes of CTCs. CONCLUSION: ZEB1-activated Notch1 promotes malignant phenotypes of CTCs in LUSC and indicates poor prognosis.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroARNs , Células Neoplásicas Circulantes , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Carcinoma de Células Escamosas/patología , Pulmón , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica/genética , MicroARNs/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Receptor Notch1RESUMEN
Resumen La vía de señalización Notch es una vía conservada evolutivamente y está involucrada en el control de diversos eventos durante el desarrollo de las células eucariotas. Esta vía se ha relacionado con la expresión y la diferenciación de las células inmunes; por lo tanto, su activación es fundamental en la expresión de la respuesta inmune innata y adquirida, que permite a los mamíferos defenderse frente antígenos externos.
Abstract The Notch signaling pathway is evolutionarily preserved and is involved in the control of several events during the development of eukaryotic cells. This pathway has been linked to expression and differentiation of immune cells, therefore it´s activation is critical in the expression of the innate immune and acquired response that allows mammals to defend themselves against external antigens.