NR2F2 plays a major role in insulin-induced epithelial-mesenchymal transition in breast cancer cells

• Published in: BMC cancer 2020-07, Vol.20 (1), p.626-626, Article 626
• Main Authors: Xia, Baili, Hou, Lijun, Kang, Huan, Chang, Wenhui, Liu, Yi, Zhang, Yanli, Ding, Yi
• Format: Article
• Language: English
• Subjects: Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer metastasis; Cancer treatment; Cell adhesion & migration; Cell growth; Cell migration; Cell Movement - genetics; COUP Transcription Factor II - genetics; COUP Transcription Factor II - metabolism; Development and progression; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - metabolism; E-cadherin; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Hyperinsulinemia; Hyperinsulinism - blood; Hyperinsulinism - epidemiology; Hyperinsulinism - etiology; Hyperinsulinism - metabolism; Insulin; Insulin - blood; Insulin - metabolism; Insulin glargine; Invasion metastasis; Lymphatic system; MCF-7 Cells; Mesenchyme; Metastases; Metastasis; Migration; N-Cadherin; Neoplasm Invasiveness - genetics; NR2F2; Polymerase chain reaction; Protein expression; Proteins; Risk Factors; Scientific equipment industry; Statistical analysis; Stem cells; Tumor cell lines; Type 2 diabetes; Vimentin
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-020-07107-6

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. 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. 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. These results suggest that NR2F2 plays a critical role in insulin-mediated breast cancer cell invasion, migration through its effect on EMT.