NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells

Zhong, Ying; Shen, Songjie; Zhou, Yidong; Mao, Feng; Lin, Yanwei; Guan, Jinghong; Xu, Yali; Zhang, Shu; Liu, Xu; Sun, Qiang

doi:10.2147/ott.s109606

Cited by 65 publications

(45 citation statements)

References 33 publications

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“…The level of NOTCH1 is significantly associated with TNM stage, metastasis, and triple-negative breast cancer, indicating that the protein is involved in metastasis and closely related to breast cancer stem cells. 42 FYN, a member of the Src family kinase (SFK), is overexpressed in various cancer types and associated with cell motility and proliferation. FYN enhances the expression of epithelial-mesenchymal transition (EMT)-related transcription factors, supporting the theory that EMT participates in FYN-induced breast carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses

Fang

Wang

et al. 2017

Tumour Biol.

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Gastric cancer is one of the most common tumors of the digestive system. Here, analysis of the expression profiles of circular RNAs in advanced gastric adenocarcinoma and adjacent normal mucosa tissues revealed differential expression of 306 circular RNAs, among which 273 were predicted to exert regulatory effects on target microRNAs. The downstream pathway networks of circular RNA-microRNA were mapped and the node genes were identified. In particular, we found that the expression of hsa_circ_0058246 was elevated in tumor specimens of patients with poor clinical outcomes. Our collective findings indicate that circular RNAs play a critical role in gastric cancer tumorigenesis. Data from this study provide a new perspective on the molecular pathways underlying metastasis and recurrence of gastric cancer and highlight potential therapeutic targets that may contribute to more effective diagnosis and treatment of the disease.

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Section: Discussionmentioning

confidence: 99%

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses

Fang

Wang

et al. 2017

Tumour Biol.

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“…Elevated levels of NR1 and NR4 were reported in the early breast cancer lesions, ductal carcinoma in situ (DCIS), and the triple negative breast cancer tumors [205,206]. Elevated levels of NR1 and JAG1 were correlated with poor patient prognosis, and shorter disease-free survival [207][208][209][210][211][212]. Although NR3 gene amplification was observed in breast cancer specimens at a low frequency [213], higher expression of NR3 was associated with improved recurrence-free survival in luminal A, luminal B and basal-like subtypes of breast cancers except for the HER2 overexpressing subtype [88].…”

Section: Notch Signaling In Breast Carcinogenesismentioning

confidence: 99%

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Bhat

Sun

Weger

et al. 2016

Stem Cells and Development

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The evolutionarily conserved Notch and Wnt signaling pathways have demonstrated roles in normal mammary gland development and in breast carcinogenesis. We previously reported that in human mammary gland, signaling through NOTCH3 alone regulates the commitment of the undifferentiated bipotential progenitors to the luminal cell fate, indicating that NOTCH3 may regulate the expression of unique genes apart from the other Notch receptors. In this study, we used gain of function and loss of function experiments and found that a Wnt signaling receptor, Frizzled7 (FZD7), is a unique and nonredundant target of NOTCH3 in human breast epithelial cells. Interestingly, neither the constitutively active forms of NOTCH1-2, 4 nor loss of expression of these receptors were able to alter expression of FZD7 in human breast epithelial cells. We further show that FZD7-expressing cells are found more frequently in the luminal progenitor-enriched subpopulation of cells obtained from breast reduction samples compared with the undifferentiated bipotent progenitors. Also, we show that NOTCH3-induced expression of FZD7 occurs in the absence of CSL (CBF1-Suppressor of Hairless-Lag-1). Our data suggest that noncanonical Notch signaling through NOTCH3 could modulate Wnt signaling via FZD7 and in this way, might be involved in luminal cell differentiation.

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“…china of EMT and cSc maintenance (9). The abnormal activation of Notch signaling has been found to be associated with tumor development and progression in breast cancer (10,11). In mammals, there are four different Notch receptors and five known ligands, which have been implicated in tumorigenesis (10).…”

Section: Introductionmentioning

confidence: 99%

“…In mammals, there are four different Notch receptors and five known ligands, which have been implicated in tumorigenesis (10). Increased expression levels of Notch receptors and their ligands in breast cancer tissues have been observed compared with levels in normal control tissues (11). Notch receptors are considered to be breast oncogenes partly due to the fact that the overexpression of Notch1 or Notch 4 can lead to the formation of spontaneous murine mammary tumors in vivo (12).…”

Section: Introductionmentioning

confidence: 99%

Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways

Cao

Yang

et al. 2018

Int J Mol Med

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Breast cancer is a leading cause of mortality among women with cancer worldwide. Quercetin‑3‑methyl ether, a natural compound occurring in various plants, has been indicated to have potent anticancer activity. Breast cancer cell growth and survival were examined by CCK‑8 and colony formation assay, whilst cell cycle and apoptosis were determined by flow cytometry. Cell invasion and migration were assessed by wound‑healing assay and Transwell assay. Cancer stem cell formation was analyzed by mammosphere formation assay and related signaling pathways were detected by western blotting. In the present study, it was observed that treatment with quercetin‑3‑methyl ether significantly inhibited cell growth, induced apoptosis and cell cycle arrest at the G2‑M phase, and suppressed invasion and migration in human breast cancer cells, including the triple negative MDAMB‑231 cell line, and the estrogen receptor‑positive/progesterone receptor‑positive/human epidermal growth factor receptor 2‑negative MCF‑7 and T47D cell lines. This compound also markedly suppressed the epithelial‑mesenchymal transition process as evidenced by the upregulated expression of E‑cadherin, and the concomitant downregulated expression of vimentin and MMP‑2. Furthermore, it was demonstrated that quercetin‑3‑methyl ether treatment inhibited mammosphere formation and the expression of the stemness‑related genes, SRY‑box 2 and Nanog. Mechanistically, this compound decreased the expression of Notch1, and induced the phosphorylation of phosphoinositide 3‑kinase (PI3K) and Akt. It also attenuated the human insulin growth factor 1‑induced phosphorylation of PI3K, Akt and glycogen synthase kinase β. Additionally, the combination of quercetin‑3‑methyl ether and a secretase inhibitor (DAPT) exhibited additive suppression of the expression of Notch1, PI3K, Akt and mammalian target of rapamycin and a more marked inhibitory effect on cell proliferation and colony formation compared with either drug alone. Treatment with quercetin‑3‑methyl ether alone markedly suppressed the levels of tri‑methyl histone H3 (Lys27), but had no effect on the expression of enhancer of zeste homolog 2. Overall, these findings indicated that quercein‑3‑methyl ether may be a potential therapeutic compound for the treatment of triple negative and hormone‑sensitive breast cancer.

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NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells

Cited by 65 publications

References 33 publications

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses

Circular RNAs play an important role in late-stage gastric cancer: Circular RNA expression profiles and bioinformatics analyses

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Quercetin‑3‑methyl ether suppresses human breast cancer stem cell formation by inhibiting the Notch1 and PI3K/Akt signaling pathways

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