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Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling
The recruitment of vascular endothelial cells from the tumor microenvironment (TME) to promote angiogenesis plays key roles in the progression of renal cell carcinoma (RCC). The potential impact of immune cells in the TME on RCC angiogenesis, however, remains unclear. Here, we found that recruitment...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442425/ https://www.ncbi.nlm.nih.gov/pubmed/28114284 http://dx.doi.org/10.1038/onc.2016.442 |
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author | Chen, Y Li, C Xie, H Fan, Y Yang, Z Ma, J He, D Li, L |
author_facet | Chen, Y Li, C Xie, H Fan, Y Yang, Z Ma, J He, D Li, L |
author_sort | Chen, Y |
collection | PubMed |
description | The recruitment of vascular endothelial cells from the tumor microenvironment (TME) to promote angiogenesis plays key roles in the progression of renal cell carcinoma (RCC). The potential impact of immune cells in the TME on RCC angiogenesis, however, remains unclear. Here, we found that recruitment of mast cells resulted in increased RCC angiogenesis in both in vitro cell lines and in vivo mouse models. Mechanistic analyses revealed that RCC recruited mast cells by modulating PI3K→AKT→GSK3β→AM signaling. A clinical survey of human RCC samples also showed that higher expression of the PI3K→AKT→GSK3β→AM signaling pathway correlated with increased angiogenesis. Interruption of PI3K→AKT→GSK3β→AM signaling via specific inhibitors led to decreased recruitment of mast cells, and targeting this infiltrating mast cell-related signaling via an AKT-specific inhibitor suppressed RCC angiogenesis in xenograft mouse models. Together, these results identified a novel role of infiltrating mast cells in RCC angiogenesis and metastasis and suggest a new strategy for treating RCC by targeting this newly identified signaling pathway. |
format | Online Article Text |
id | pubmed-5442425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54424252017-06-02 Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling Chen, Y Li, C Xie, H Fan, Y Yang, Z Ma, J He, D Li, L Oncogene Original Article The recruitment of vascular endothelial cells from the tumor microenvironment (TME) to promote angiogenesis plays key roles in the progression of renal cell carcinoma (RCC). The potential impact of immune cells in the TME on RCC angiogenesis, however, remains unclear. Here, we found that recruitment of mast cells resulted in increased RCC angiogenesis in both in vitro cell lines and in vivo mouse models. Mechanistic analyses revealed that RCC recruited mast cells by modulating PI3K→AKT→GSK3β→AM signaling. A clinical survey of human RCC samples also showed that higher expression of the PI3K→AKT→GSK3β→AM signaling pathway correlated with increased angiogenesis. Interruption of PI3K→AKT→GSK3β→AM signaling via specific inhibitors led to decreased recruitment of mast cells, and targeting this infiltrating mast cell-related signaling via an AKT-specific inhibitor suppressed RCC angiogenesis in xenograft mouse models. Together, these results identified a novel role of infiltrating mast cells in RCC angiogenesis and metastasis and suggest a new strategy for treating RCC by targeting this newly identified signaling pathway. Nature Publishing Group 2017-05-18 2017-01-23 /pmc/articles/PMC5442425/ /pubmed/28114284 http://dx.doi.org/10.1038/onc.2016.442 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Article Chen, Y Li, C Xie, H Fan, Y Yang, Z Ma, J He, D Li, L Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title | Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title_full | Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title_fullStr | Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title_full_unstemmed | Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title_short | Infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating PI3K→AKT→GSK3β→AM signaling |
title_sort | infiltrating mast cells promote renal cell carcinoma angiogenesis by modulating pi3k→akt→gsk3β→am signaling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442425/ https://www.ncbi.nlm.nih.gov/pubmed/28114284 http://dx.doi.org/10.1038/onc.2016.442 |
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