NADPH oxidase 1 as a new regulator of the WNT pathway and the protective effect of vitamin D in colorectal cancer
| العنوان: | NADPH oxidase 1 as a new regulator of the WNT pathway and the protective effect of vitamin D in colorectal cancer |
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| المؤلفون: | Navarro-Ramírez, Eliezer, Román-Fernández, José Luis, Gutiérrez-Salmerón, María, Ramírez-Sánchez, Ana, Sánchez-De La Cruz, Alberto, Chocarro-Calvo, Ana, Martin-Orozco, Rosa, Fiuza, C., Larriba, María Jesús, Muñoz Terol, Alberto, García-Martínez, José Manuel, García-Jiménez, Custodia |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| سنة النشر: | 2021 |
| الوصف: | Trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 22 de julio de 2021. Worldwide, colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-associated mortality, with an estimated increase in global prevalence of 60% by 2030 (1,2). Mutational inactivation of adenomatous polyposis coli (APC) is the hallmark of CRC and leads to an overactivation of WNT signaling that favors the development and progression of CRC (3). Large epidemiological studies suggest that the diabetic population is at increased risk for site-specific cancers, including CRC (4). Our laboratory has shown that hyperglycemia induces the accumulation of ROS in CRC but not healthy cells, driving the activation of a newly described ROS/AMPK/EP300 axis that enhances Wnt/b-catenin signaling. Increased EP300 leads to increased acetylation of β-catenin at K354, a requirement for nuclear accumulation and transcriptional activation of WNT target genes (5,6). The critical role driven by ROS suggest a possible involvement of the NADPH oxidases (NOX family, as a source of ROS. Specifically, NOX 1 and NOX 4 are expressed in colon epithelial cells, and their overexpression in CRC cells promotes cell proliferation and invasiveness (7,8,9,10). Our results indicate that hyperglycemia significantly increases NOX1 levels, in correlation with increased ROS production in CRC cells, suggesting a possible regulation of the ROS/ AMPK/EP300 axis by NOX1. Antioxidant mechanisms dealing with NOX1-induced ROS should be effective against CRC. Vitamin D (1α, 25-dihydroxyvitamin D3) is a powerful antioxidant that inhibits proliferation and promotes differentiation of CRC cells at least partially through inhibition of Wnt/β-catenin signalling. Consequently, vitamin D deficiency is associated with poor survival to CRC (11,12). Our results indicate that vitamin D causes a reduction in the levels and / or activity of some members of the NOX family by turning off the ROS/AMPK/EP300/β-catenin axis and its proliferative and tumorigenic effects. The data suggest a new antitumor mechanism of vitamin D linked to its anti-oxidant action. Our results integrate independent epidemiological links between vitamin D deficiency, diabetes and cancer in one overarching and unifying mechanism. |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::3963271a43b5aeb940c62dc53a5b2c46 http://hdl.handle.net/10261/265859 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.dedup.wf.001..3963271a43b5aeb940c62dc53a5b2c46 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |