ArticleBMC cancer2013
HRG-β1-driven ErbB3 signaling induces epithelial-mesenchymal transition in breast cancer cells.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- Trial
- Endocervical adenocarcinoma of the gastric type: a case report and literature review.Frontiers in oncology · 2025Article
- Transcriptomic profiling on localized gastric cancer identified CPLX1 as a gene promoting malignant phenotype of gastric cancer and a predictor of recurrence after surgery and subsequent chemotherapy.Journal of gastroenterology · 2022Article
- Breast cancer circulating tumor cells with mesenchymal features-an unreachable target?Cellular and molecular life sciences : CMLS · 2022Review
- Immunohistochemical and genetic characteristics of HPV-associated endocervical carcinoma with an invasive stratified mucin-producing carcinoma (ISMC) component.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2021Article
- Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts.Oncogene · 2021Article
- 5-Aza-2'-deoxycytidine advances the epithelial-mesenchymal transition of breast cancer cells by demethylatingJournal of cell science · 2020Article
- Periodontal pathogens promote epithelial-mesenchymal transition in oral squamous carcinoma cells in vitro.Cell adhesion & migration · 2018Article
- Pseudoscaffolds and anchoring proteins: the difference is in the details.Biochemical Society transactions · 2017Review
- EGF induces epithelial-mesenchymal transition through phospho-Smad2/3-Snail signaling pathway in breast cancer cells.Oncotarget · 2016Article
- Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1α.Molecular and cellular biology · 2016Article
- Chitooligosaccharide Inhibits Scar Formation and Enhances Functional Recovery in a Mouse Model of Sciatic Nerve Injury.Molecular neurobiology · 2016Article
- Anti-cancer effect of metformin by suppressing signaling pathway of HER2 and HER3 in tamoxifen-resistant breast cancer cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- MiRNA-10b sponge: An anti-breast cancer study in vitro.Oncology reports · 2016Article
- Targeted Inhibition of Snail Activity in Breast Cancer Cells by Using a Co(III) -Ebox Conjugate.Chembiochem : a European journal of chemical biology · 2015Article
- PYK2 integrates growth factor and cytokine receptors signaling and potentiates breast cancer invasion via a positive feedback loop.Oncotarget · 2015Article
- Ligand-associated ERBB2/3 activation confers acquired resistance to FGFR inhibition in FGFR3-dependent cancer cells.Oncogene · 2015Article
- Article
- Review
- Non-viral nanocarriers for siRNA delivery in breast cancer.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHeregulin (HRG; also known as neuregulin) is a ligand for ErbB3. One of its isotypes, HRG-β1, binds to ErbB3 and forms heterodimers with other ErbB family members, thereby enhancing the proliferation and tumorigenesis of breast cancer cells. HRG stimulation may contribute to the progression of epithelial-mesenchymal transition (EMT) and tumor metastasis in breast cancer. Majority of studies regarding EMT has been concentrated on TGF-β signaling. Therefore, we investigated whether the HRG-β1 and ErbB3 activate Smad2 signaling during process of EMT in breast cancer cells.
methodsThe SK-BR-3 and MCF7 breast cancer cell lines were used. The expressions of phospho-Smad2 and EMT markers were observed by western blotting and immunofluorescence assays after treatment with HRG-β1. The cell motility and invasiveness were determined by wound healing and matrigel invasion assays. Smad2 and ErbB3 small interfering RNA (siRNA) transfections were performed to assess the involvement of ErbB3 and Smad2 in HRG-β1-induced EMT.
resultsHRG-β1 induced EMT through activation of Smad2. The expression of E-cadherin was decreased after HRG-β1 treatment, while the expressions of Snail, vimentin, and fibronectin were increased. The HRG-β1-induced expressions of Snail, vimentin, and fibronectin, and nuclear colocalization of phospho-Smad2 and Snail were inhibited by pretreatment with a PI3k inhibitor, LY294002, or two phospho-Smad2 inhibitors, PD169316 or SB203580 and cancer cell migration by HRG-β1 was inhibited. Knockdown of Smad2 by siRNA transfection suppressed the expressions of Snail and fibronectin in response to HRG-β1 stimulation and knockdown of ErbB3 suppressed the expressions of phospho-Smad2, Snail, and fibronectin induced by HRG-β1, whereas E-cadherin was increased compared with control siRNA-transfected cells. Knockdown of ErbB3 and Smad2 also decreased SK-BR-3 and MCF7 cell invasion.
conclusionsOur data suggest that HRG-β1 and ErbB3 induce EMT, cancer cell migration and invasion through the PI3k/Akt-phospho-Smad2-Snail signaling pathway in SK-BR-3 and MCF7 breast cancer cells.
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