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Increase in ADAR1p1...
Increase in ADAR1p110 activates the canonical Wnt signaling pathway associated with aggressive phenotype in triple negative breast cancer cells
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Morales, Fernanda (author)
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Pérez, Paola (author)
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Tapia, Julio C. (author)
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Lobos-González, Lorena (author)
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Manuel Herranz, José (author)
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Guevara, Francisca (author)
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Rojas de Santiago, Pamela (author)
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Palacios, Esteban (author)
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Andaur, Rodrigo (author)
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- Sagredo, Eduardo A. (author)
- Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Universidad de Chile, Chile; Center of Excellence in Precision Medicine, Chile
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Marcelain, Katherine (author)
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Armisén, Ricardo (author)
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 819
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Triple-negative breast cancer (TNBC) represents a challenge in the search for new therapeutic targets. TNBCs are aggressive and generate resistance to chemotherapy. Tumors of TNBC patients with poor prognosis present a high level of adenosine deaminase acting on RNA1 (ADAR1). We explore the connection of ADAR1 with the canonical Wnt signaling pathway and the effect of modulation of its expression in TNBC. Expression data from cell line sequencing (DepMap) and TCGA samples were downloaded and analyzed. We lentivirally generated an MDA-MB-231 breast cancer cell line that overexpress (OE) ADAR1p110 or an ADAR knockdown. Abundance of different proteins related to Wnt/β-catenin pathway and activity of nuclear β-catenin were analyzed by Western blot and luciferase TOP/FOP reporter assay, respectively. Cell invasion was analyzed by matrigel assay. In mice, we study the behavior of tumors generated from ADAR1p110 (OE) cells and tumor vascularization immunostaining were analyzed. ADAR1 connects to the canonical Wnt pathway in TNBC. ADAR1p110 overexpression decreased GSK-3β, while increasing active β-catenin. It also increased the activity of nuclear β-catenin and increased its target levels. ADAR1 knockdown has the opposite effect. MDA-MB-231 ADAR1 (OE) cells showed increased capacity of invasion. Subsequently, we observed that tumors derived from ADAR1p110 (OE) cells showed increased invasion towards the epithelium, and increased levels of Survivin and CD-31 expressed in vascular endothelial cells. These results indicate that ADAR1 overexpression alters the expression of some key components of the canonical Wnt pathway, favoring invasion and neovascularization, possibly through activation of the β-catenin, which suggests an unknown role of ADAR1p110 in aggressiveness of TNBC tumors.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- ADAR1
- TNBC
- Canonical Wnt pathway
- Cell invasion
- Breast cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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Gene
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- By the author/editor
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Morales, Fernand ...
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Pérez, Paola
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Tapia, Julio C.
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Lobos-González, ...
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Manuel Herranz, ...
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Guevara, Francis ...
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show more...
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Rojas de Santiag ...
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Palacios, Esteba ...
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Andaur, Rodrigo
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Sagredo, Eduardo ...
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Marcelain, Kathe ...
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Armisén, Ricardo
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
- Articles in the publication
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Gene
- By the university
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Stockholm University