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ITGA5 promotes tumor angiogenesis in cervical cancer
PURPOSE: Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. METHODS: ITGA5 protein expression was detected in 155 human...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242342/ https://www.ncbi.nlm.nih.gov/pubmed/36999964 http://dx.doi.org/10.1002/cam4.5873 |
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author | Xu, Xiaohan Shen, Lulu Li, Wenhan Liu, Xiaoli Yang, Ping Cai, Jing |
author_facet | Xu, Xiaohan Shen, Lulu Li, Wenhan Liu, Xiaoli Yang, Ping Cai, Jing |
author_sort | Xu, Xiaohan |
collection | PubMed |
description | PURPOSE: Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. METHODS: ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5‐associated differentially expressed genes. Analyses of single‐cell RNA‐seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT‐PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. RESULTS: High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5‐associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5‐targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K‐Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p‐AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1‐targeting siRNA showed fibronectin may play a critical role on ITGA5‐mediated angiogenesis. CONCLUSION: ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer. |
format | Online Article Text |
id | pubmed-10242342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102423422023-06-07 ITGA5 promotes tumor angiogenesis in cervical cancer Xu, Xiaohan Shen, Lulu Li, Wenhan Liu, Xiaoli Yang, Ping Cai, Jing Cancer Med Research Articles PURPOSE: Integrins are critical to cancer progression. Integrin alpha 5 (ITGA5) is correlated with the prognosis of cervical cancer patients. However, whether ITGA5 plays an active role in cervical cancer progression or not remains unknown. METHODS: ITGA5 protein expression was detected in 155 human cervical cancer tissues by immunohistochemistry. Data from The Cancer Genome Atlas were utilized to identify risk factors for the overall survival of cervical cancer patients and ITGA5‐associated differentially expressed genes. Analyses of single‐cell RNA‐seq based on Gene Expression Omnibus datasets were performed to show the coexpression of ITGA5 and angiogenesis factors. Tube formation assay, 3D spheroid sprout assay, qRT‐PCR, Western Blotting, ELISA, and immunofluorescence were conducted to explore the angiogenic function of ITGA5 in vitro and underlying mechanisms. RESULTS: High ITGA5 level was significantly correlated with increased risk in terms of overall survival and advanced disease stage in cervical cancer patients. ITGA5‐associated differentially expressed genes linked ITGA5 to angiogenesis, and immunohistochemistry showed a positive correlation between ITGA5 and microvascular density in cervical cancer tissues. Moreover, tumor cells transfected with ITGA5‐targeting siRNA decreased ability to promote endothelial tube formation in vitro. ITGA5/VEGFA coexpression was observed in a tumor cell subpopulation and the decreased endothelial angiogenesis by downregulating ITGA5 could be reversed by VEGFA. Bioinformatics analysis highlighted the PI3K‐Akt signaling pathway as downstream of ITGA5. Downregulation of ITGA5 in tumor cells significantly decreased p‐AKT and VEGFA levels. Fibronectin (FN1) coated cells or transfected with FN1‐targeting siRNA showed fibronectin may play a critical role on ITGA5‐mediated angiogenesis. CONCLUSION: ITGA5 promotes angiogenesis and possibly be a potential predictive biomarker for poor survival of patients in cervical cancer. John Wiley and Sons Inc. 2023-03-31 /pmc/articles/PMC10242342/ /pubmed/36999964 http://dx.doi.org/10.1002/cam4.5873 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Xu, Xiaohan Shen, Lulu Li, Wenhan Liu, Xiaoli Yang, Ping Cai, Jing ITGA5 promotes tumor angiogenesis in cervical cancer |
title |
ITGA5 promotes tumor angiogenesis in cervical cancer |
title_full |
ITGA5 promotes tumor angiogenesis in cervical cancer |
title_fullStr |
ITGA5 promotes tumor angiogenesis in cervical cancer |
title_full_unstemmed |
ITGA5 promotes tumor angiogenesis in cervical cancer |
title_short |
ITGA5 promotes tumor angiogenesis in cervical cancer |
title_sort | itga5 promotes tumor angiogenesis in cervical cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242342/ https://www.ncbi.nlm.nih.gov/pubmed/36999964 http://dx.doi.org/10.1002/cam4.5873 |
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