Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42

Tian, Yuan; Zhang, Peipei; Mou, Yajun; Yang, Wenxiu; Zhang, Mengjie; Li, Qing; Dou, Xiaowei

doi:10.1038/s41420-023-01450-w

Cited by 6 publications

(2 citation statements)

References 59 publications

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“…To evaluate the function of tumoral Notch4, we first determined tumor cell and stromal cell types that express Notch4. Prior studies have indicated that Notch4 can be expressed by tumor endothelium, immune cells, and some cancer cells ( 24 – 27 ). We examined the presence of Notch4 by IF staining of tumors derived from Calu-6 non–small cell lung carcinoma (NSCLC) and MDA-MB-231 triple-negative breast carcinoma implanted into BALB/c nude mice.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium

Eng,

Kato,

Adachi

et al. 2024

Cancer Research Communications

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Endothelial Notch signaling is critical for tumor angiogenesis. Notch1 blockade can interfere with tumor vessel function but causes tissue hypoxia and gastrointestinal toxicity. Notch4 is primarily expressed in endothelial cells, where it may promote angiogenesis; however, effective therapeutic targeting of Notch4 has not been successful. We developed highly specific Notch4-blocking antibodies, 6-3-A6 and humanized E7011, allowing therapeutic targeting of Notch4 to be assessed in tumor models. Notch4 was expressed on tumor endothelial cells in multiple cancer models, and endothelial expression was associated with response to E7011/6-3-A6. Anti-Notch4 treatment significantly delayed tumor growth in mouse models of breast, skin, and lung cancer. Enhanced tumor inhibition occurred when anti-Notch4 treatment was used in combination with chemotherapeutics. Endothelial transcriptomic analysis of murine breast tumors treated with 6-3-A6 identified significant changes in pathways of vascular function but caused only modest change in canonical Notch signaling. Analysis of early and late treatment timepoints revealed significant differences in vessel area and perfusion in response to anti-Notch4 treatment. We conclude that targeting Notch4 improves tumor growth control through endothelial intrinsic mechanisms.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium

Eng,

Kato,

Adachi

et al. 2024

Cancer Research Communications

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“…Suppressing Notch 3 has been investigated to limit metastasis and enhance cell response to chemotherapy [ 60 , 61 ], as well as affect the tumour microenvironment and decrease activation of cancer-associated fibroblasts [ 62 ]. Notch 4’s role in breast cancer is not well-defined compared to other Notch receptors, but has been linked to angiogenesis and vascularization, which may influence tumour growth and metastasis [ 63 ]. Expression of Notch 4 is associated with the basal-like subtype of breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Analysing potent biomarkers along phytochemicals for breast cancer therapy: an in silico approach

Shekar,

Vuong,

Kaur

2023

Breast Cancer Res Treat

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Purpose This research focused on the identification of herbal compounds as potential anti-cancer drugs, especially for breast cancer, that involved the recognition of Notch downstream targets NOTCH proteins (1–4) specifically expressed in breast tumours as biomarkers for prognosis, along with P53 tumour antigens, that were used as comparisons to check the sensitivity of the herbal bio-compounds. Methods After investigating phytochemical candidates, we employed an approach for computer-aided drug design and analysis to find strong breast cancer inhibitors. The present study utilized in silico analyses and protein docking techniques to characterize and rank selected bio-compounds for their efficiency in oncogenic inhibition for use in precise carcinomic cell growth control. Results Several of the identified phytocompounds found in herbs followed Lipinski’s Rule of Five and could be further investigated as potential medicinal molecules. Based on the Vina score obtained after the docking process, the active compound Epigallocatechin gallate in green tea with NOTCH (1–4) and P53 proteins showed promising results for future drug repurposing. The stiffness and binding stability of green tea pharmacological complexes were further elucidated by the molecular dynamic simulations carried out for the highest scoring phytochemical ligand complex. Conclusion The target-ligand complex of green tea active compound Epigallocatechin gallate with NOTCH (1–4) had the potential to become potent anti-breast cancer therapeutic candidates following further research involving wet-lab experiments.

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Advances in targets in inflammatory breast cancer

Iwase,

Wang,

Thi Hanh Phi

et al. 2024

International Review of Cell and Molecular Biology

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Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42

Cited by 6 publications

References 59 publications

Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium

Inhibition of Notch4 Using Novel Neutralizing Antibodies Reduces Tumor Growth in Murine Cancer Models by Targeting the Tumor Endothelium

Analysing potent biomarkers along phytochemicals for breast cancer therapy: an in silico approach

Advances in targets in inflammatory breast cancer

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