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...

Full description

Bibliographic Details
Main Authors: Baili Xia, Lijun Hou, Huan Kang, Wenhui Chang, Yi Liu, Yanli Zhang, Yi Ding
Format: Article
Language:English
Published: BMC 2020-07-01
Series:BMC Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12885-020-07107-6
_version_ 1830430862350483456
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
format Article
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
record_format Article
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
work_keys_str_mv AT bailixia nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT lijunhou nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT huankang nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT wenhuichang nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT yiliu nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT yanlizhang nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells
AT yiding nr2f2playsamajorroleininsulininducedepithelialmesenchymaltransitioninbreastcancercells