Cargando…
Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer
Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with n...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997793/ https://www.ncbi.nlm.nih.gov/pubmed/29717026 http://dx.doi.org/10.1042/BSR20180394 |
_version_ | 1783331111067189248 |
---|---|
author | Gao, Bo Guo, Lingji Luo, Donglin Jiang, Yan Zhao, Jianjie Mao, Chengyi Xu, Yan |
author_facet | Gao, Bo Guo, Lingji Luo, Donglin Jiang, Yan Zhao, Jianjie Mao, Chengyi Xu, Yan |
author_sort | Gao, Bo |
collection | PubMed |
description | Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression. |
format | Online Article Text |
id | pubmed-5997793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59977932018-06-13 Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer Gao, Bo Guo, Lingji Luo, Donglin Jiang, Yan Zhao, Jianjie Mao, Chengyi Xu, Yan Biosci Rep Research Articles Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression. Portland Press Ltd. 2018-06-12 /pmc/articles/PMC5997793/ /pubmed/29717026 http://dx.doi.org/10.1042/BSR20180394 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Gao, Bo Guo, Lingji Luo, Donglin Jiang, Yan Zhao, Jianjie Mao, Chengyi Xu, Yan Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title | Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title_full | Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title_fullStr | Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title_full_unstemmed | Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title_short | Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer |
title_sort | steroid receptor coactivator-1 interacts with nf-κb to increase vegfc levels in human thyroid cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997793/ https://www.ncbi.nlm.nih.gov/pubmed/29717026 http://dx.doi.org/10.1042/BSR20180394 |
work_keys_str_mv | AT gaobo steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT guolingji steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT luodonglin steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT jiangyan steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT zhaojianjie steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT maochengyi steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer AT xuyan steroidreceptorcoactivator1interactswithnfkbtoincreasevegfclevelsinhumanthyroidcancer |