AIB1 Cooperates with ERα to Promote Epithelial Mesenchymal Transition in Breast Cancer through SNAI1 Activation

Wang, Miao; Zhao, Feng; Li, Shujing; Chang, Alan K.; Jia, Zhaojun; Chen, Yixuan; Xu, Feihong; Pan, Hongming; Wu, Harry X.

doi:10.1371/journal.pone.0065556

Cited by 30 publications

(41 citation statements)

References 39 publications

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“…3). It has also been found that downregulation of the epithelial marker E-cadherin induced the expression of various mesenchymal markers, such as Snail and vimentin, during EMT (25). Consistent with these observations, we found that overexpression of RUNX3 significantly inhibited motility and invasiveness in CRC cells.…”

Section: Discussionsupporting

confidence: 91%

RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

et al. 2016

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Recent studies have determined that inactivation of runt‑related transcription factor 3 (RUNX3) expression is highly associated with lymph node metastasis and poor prognosis in various types of cancer. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). Firstly, we found that the reduction in expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with tumor-node-metastasis (TNM) stage. Secondly, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Finally, we found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. All in all, our findings may provide insight into the development of RUNX3 for CRC metastasis diagnostics and therapeutics.

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Section: Discussionsupporting

confidence: 91%

RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

et al. 2016

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“…Multiple lines of evidence suggest that different mechanisms are used in SRC-3-mediated cancer cell migration and invasion in a cancer-specific manner (10,11,(27)(28)(29). An inverse correlation between SRC-3 and E-cadherin has been reported in human pancreatic adenocarcinoma, implying that SRC-3 regulates E-cadherin directly or indirectly (27).…”

Section: Discussionmentioning

confidence: 99%

“…An inverse correlation between SRC-3 and E-cadherin has been reported in human pancreatic adenocarcinoma, implying that SRC-3 regulates E-cadherin directly or indirectly (27). By co-activating estrogen receptor α (ERα) in T47D breast cancer cells, SRC-3 also transcriptionally upregulates Snail, which directly represses E-cadherin (28). However, SRC-3 overexpression is not associated with the levels of ERα in UBC tissue samples (10), and urothelial specific ERα-knockout enhanced carcinogen-induced UBC development, suggesting that ERα behaves as a tumor suppressor in UBC (30).…”

Section: Discussionmentioning

confidence: 99%

Honokiol inhibits bladder cancer cell invasion through repressing SRC-3 expression and epithelial-mesenchymal transition

et al. 2017

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Abstract. Urinary bladder cancer (UBC) is one of the most common urological cancer types. Muscle invasive bladder cancer possesses high propensity for metastasis with poor prognosis. Honokiol is a lignan isolated from Magnolia officinalis with high bioavailability and potent anticancer effects. The results of the present study demonstrated that honokiol significantly inhibited UBC cell migration and invasion in a dose-dependent manner compared with the vehicle-treated control group. In addition, honokiol treatment suppressed epithelial-mesenchymal transition by induction of E-cadherin and repression of N-cadherin. Honokiol was capable of significantly downregulating the expression of cell invasion-associated genes, steroid receptor coactivator-3 (SRC-3), matrix metalloproteinase (MMP)-2 and Twist1. Notably, the inhibition of UBC cell invasion by honokiol was reversed by reintroduction of oncoprotein SRC-3 expression, with the restoration of MMP-2 and Twist1, and reduction of E-cadherin expression. Furthermore, the results of the luciferase assay confirmed that SRC-3 could regulate Twist1 promoter activity. Taken together, the results of the present study suggest that honokiol is a promising agent against UBC cell invasion via downregulation of SRC-3 and its target genes. IntroductionUrinary bladder cancer (UBC) is one of the most common types of malignant tumor in the United States, with an estimated 58,950 new cases and 11,820 UBC-associated mortalities in 2016 (1). Data between 2005 and 2011 in USA revealed that the 5-year survival rate for localized UBC was ~70%, whereas the rate for patients with UBC with distant lesions was ~5% (1). In China, bladder cancer prevalence ranks the 9th and the 2nd positions for the entire population, and people >65 years, respectively (2). However, current treatments, including chemotherapy and radiotherapy possess limited effects on muscle invasive bladder cancer (>stage 2). Therefore, studies investigating the underlying molecular mechanisms of UBC development and the development of efficacious therapeutic reagents for UBC, particularly for patients with invasive cancer are warranted.Steroid receptor coactivator-3 (SRC-3) and alias amplification in breast cancer 1 belong to the p160 steroid receptor coactivator family (3). Amplification and/or overexpression of SRC-3 have been implicated in steroid-targeted tissues, including in breast and prostate cancer (4-6), and in non-steroid-targeted tissues, including lung and bladder cancer (7-10). Accumulating evidence indicates that SRC-3 can activate steroid and non-steroid receptors. For example, SRC-3 serves as a co-activator for transcription factors ETS variant 4 (PEA3) and JunB proto-oncogene AP-1 transcription factor subunit, which leads to the upregulation of matrix metalloproteinase (MMP)-2, and -13 in androgen receptor-null PC3 prostate cancer cells (11). Furthermore, SRC-3 facilitates E2F transcription factor 1 (E2F1) to promote the proliferation of breast cancer cells (12). Previous studies, including our previous study,...

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“…Estradiol also promotes the proliferation of astrocytoma cells through estrogen receptor-α (ERα) and its interaction with AIB1 35. It is the fact that AIB1 interacts with ERα, and subsequently binds to ERα-binding site on the promoter of SNAI1 , a transcriptional repressor for E-cadherin, to promote the transcription of SNAI1 and repress E-cadherin expression, ultimately leading to the initiation and progression of epithelial mesenchymal transition (EMT) 36. Thus, we speculate that specific role and prognostic value of AIB1 amplification in female glioma patients may be related to sex hormones and nuclear receptor levels.…”

Section: Discussionmentioning

confidence: 99%

AIB1 Genomic Amplification Predicts Poor Clinical Outcomes in Female Glioma Patients

et al. 2016

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Amplified in breast cancer 1 (AIB1) gene, a coactivator for steroid receptor, is frequently amplified in diverse cancers and is considered as an oncogene in tumorigenesis. However, the prognostic significance of AIB1 amplification in gliomas remains totally unclear. In this study, 115 gliomas and 16 benign meningiomas as control subjects were enrolled, and the copy number of AIB1 was analyzed in these samples. In addition, we explored potential correlation of AIB1 amplification with clinicopathological characteristics and clinical outcomes of glioma patients. Our data showed that glioma samples exhibited a significantly higher AIB1 copy number than control subjects as determined by quantitative polymerase chain reaction (qPCR) approach. Moreover, univariate analysis showed that AIB1 amplification (≥3.5 copies) was strongly correlated with cancer-related death (P =0.03). Interestingly, our data revealed a significant association of AIB1 amplification with WHO grade (P =0.03), tumor recurrence (P =0.03) and survival status (P =0.03) in female patients but not in male patients. Multivariate analysis further demonstrated that AIB1 amplification was independent factor for cancer-related death in female patients. Importantly, AIB1 amplification was closely relevant to worse survival in female patients (P =0.001), but not in male patients (P =1.00). In addition, the patients with AIB1 amplification were resistant to radiotherapy. Altogether, our data demonstrate that AIB1 amplification is a common genetic event in glioma tumorigenesis, and suggest that AIB1 amplification is not only a prognostic factor for poor clinical outcomes in glioma patients, but also a predictor of radiotherapy resistance in gliomas.

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AIB1 Cooperates with ERα to Promote Epithelial Mesenchymal Transition in Breast Cancer through SNAI1 Activation

Cited by 30 publications

References 39 publications

RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

RUNX3 inhibits the metastasis and angiogenesis of colorectal cancer

Honokiol inhibits bladder cancer cell invasion through repressing SRC-3 expression and epithelial-mesenchymal transition

AIB1 Genomic Amplification Predicts Poor Clinical Outcomes in Female Glioma Patients

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