NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells
Abstract Background The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progres...
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BMC
2020-07-01
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Series: | BMC Cancer |
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Online Access: | http://link.springer.com/article/10.1186/s12885-020-07107-6 |
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author | Baili Xia Lijun Hou Huan Kang Wenhui Chang Yi Liu Yanli Zhang Yi Ding |
author_facet | Baili Xia Lijun Hou Huan Kang Wenhui Chang Yi Liu Yanli Zhang Yi Ding |
author_sort | Baili Xia |
collection | DOAJ |
description | Abstract Background The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclear receptor subfamily 2, group F, member 2 (NR2F2) has been implicated in the development of breast cancer, however its contribution to insulin-induced EMT in breast cancer remains unclear. Methods Overexpression and knockdown of NR2F2 were used in two breast cancer cell lines, MCF-7 and MDA-MB-231 to investigate potential mechanisms by which NR2F2 leads to insulin-mediated EMT. To elucidate the effects of insulin and signaling events following NR2F2 overexpression and knockdown, Cells’ invasion and migration capacity and changes of NR2F2, E-cadherin, N-cadherin and vimentin were investigated by real-time RT-PCR and western blot. Results Insulin stimulation of these cells increased NR2F2 expression levels and promoted cell invasion and migration accompanied by alterations in EMT-related molecular markers. Overexpression of NR2F2 and NR2F2 knockdown demonstrated that NR2F2 expression was positively correlated with cell invasion, migration and the expression of N-cadherin and vimentin. In contrast, NR2F2 had an inverse correlation with E-cadherin expression. In MDA-MB-231, both insulin-induced cell invasion and migration and EMT-related marker alteration were abolished by NR2F2 knockdown. Conclusions These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT. |
first_indexed | 2024-12-21T01:57:24Z |
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id | doaj.art-bc5bc4b9e7924d8a9a94f6f73ce4ee19 |
institution | Directory Open Access Journal |
issn | 1471-2407 |
language | English |
last_indexed | 2024-12-21T01:57:24Z |
publishDate | 2020-07-01 |
publisher | BMC |
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series | BMC Cancer |
spelling | doaj.art-bc5bc4b9e7924d8a9a94f6f73ce4ee192022-12-21T19:19:44ZengBMCBMC Cancer1471-24072020-07-0120111210.1186/s12885-020-07107-6NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cellsBaili Xia0Lijun Hou1Huan Kang2Wenhui Chang3Yi Liu4Yanli Zhang5Yi Ding6Department of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityDepartment of Pathophysiology, Weifang Medical UniversityAbstract Background The failure of treatment for breast cancer usually results from distant metastasis in which the epithelial-mesenchymal transition (EMT) plays a critical role. Hyperinsulinemia, the hallmark of Type 2 diabetes mellitus (T2DM), has been regarded as a key risk factor for the progression of breast cancer. Nuclear receptor subfamily 2, group F, member 2 (NR2F2) has been implicated in the development of breast cancer, however its contribution to insulin-induced EMT in breast cancer remains unclear. Methods Overexpression and knockdown of NR2F2 were used in two breast cancer cell lines, MCF-7 and MDA-MB-231 to investigate potential mechanisms by which NR2F2 leads to insulin-mediated EMT. To elucidate the effects of insulin and signaling events following NR2F2 overexpression and knockdown, Cells’ invasion and migration capacity and changes of NR2F2, E-cadherin, N-cadherin and vimentin were investigated by real-time RT-PCR and western blot. Results Insulin stimulation of these cells increased NR2F2 expression levels and promoted cell invasion and migration accompanied by alterations in EMT-related molecular markers. Overexpression of NR2F2 and NR2F2 knockdown demonstrated that NR2F2 expression was positively correlated with cell invasion, migration and the expression of N-cadherin and vimentin. In contrast, NR2F2 had an inverse correlation with E-cadherin expression. In MDA-MB-231, both insulin-induced cell invasion and migration and EMT-related marker alteration were abolished by NR2F2 knockdown. Conclusions These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT.http://link.springer.com/article/10.1186/s12885-020-07107-6Breast cancerNR2F2InsulinEpithelial-mesenchymal transitionMigrationInvasion metastasis |
spellingShingle | Baili Xia Lijun Hou Huan Kang Wenhui Chang Yi Liu Yanli Zhang Yi Ding NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells BMC Cancer Breast cancer NR2F2 Insulin Epithelial-mesenchymal transition Migration Invasion metastasis |
title | NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells |
title_full | NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells |
title_fullStr | NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells |
title_full_unstemmed | NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells |
title_short | NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells |
title_sort | nr2f2 plays a major role in insulin induced epithelial mesenchymal transition in breast cancer cells |
topic | Breast cancer NR2F2 Insulin Epithelial-mesenchymal transition Migration Invasion metastasis |
url | http://link.springer.com/article/10.1186/s12885-020-07107-6 |
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