ArticleCell death & disease2021
Notch3 inhibits cell proliferation and tumorigenesis and predicts better prognosis in breast cancer through transactivating PTEN.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Evaluating the consequences of childhood adiposity on the human plasma proteome at four timepoints across the lifecourse.Nature communications · 2026Article
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Pathological and therapeutic implications of Notch overexpression in claudin-low breast cancers.Human cell · 2026Article
- The role of Notch signalling and its crosstalk with oestrogen receptor signalling in breast cancer.Cancer metastasis reviews · 2026Review
- Integrating next-generation sequencing and artificial intelligence for the identification and validation of pathogenic variants in colorectal cancer.Frontiers in oncology · 2025Article
- Androgen receptor inhibitor ameliorates pulmonary arterial hypertension by enhancing the apoptosis level through suppressing the Notch3/Hes5 pathway.Frontiers in pharmacology · 2025Article
- NOTCH3 promotes malignant progression of bladder cancer by directly regulating SPP1 and activating PI3K/AKT pathway.Cell death & disease · 2024Article
- Functional Investigations of p53 Acetylation Enabled by Heterobifunctional Molecules.ACS chemical biology · 2024Article
- A Transcriptomic Analysis of Laryngeal Dysplasia.International journal of molecular sciences · 2024Review
- Clinicopathologic features and genomic profiling of female axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary.Journal of cancer research and clinical oncology · 2024Article
- Molecular profiling of a bladder cancer with very high tumour mutational burden.Cell death discovery · 2024Article
- NOTCH3 inhibits transcription factor ZEB1 expression and metastasis of breast cancer cells via transcriptionally upregulating miR-223.Journal of Cancer · 2024Article
- Notch3 restricts metastasis of breast cancers through regulation of the JAK/STAT5A signaling pathway.BMC cancer · 2023Article
- Proteome-wide mendelian randomization study implicates therapeutic targets in common cancers.Journal of translational medicine · 2023Article
- Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment.Medical oncology (Northwood, London, England) · 2023Review
- Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42.Cell death discovery · 2023Article
- Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Berberine governs NOTCH3/AKT signaling to enrich lung-resident memory T cells during tuberculosis.PLoS pathogens · 2023Article
- Notch3 regulates Mybl2 via HeyL to limit proliferation and tumor initiation in breast cancer.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch receptors (Notch1-4) play critical roles in tumorigenesis and metastasis of malignant tumors, including breast cancer. Although abnormal Notch activation is related to various tumors, the importance of single receptors and their mechanism of activation in distinct breast cancer subtypes are still unclear. Previous studies by our group demonstrated that Notch3 may inhibit the emergence and progression of breast cancer. PTEN is a potent tumor suppressor, and its loss of function is sufficient to promote the occurrence and progression of tumors. Intriguingly, numerous studies have revealed that Notch1 is involved in the regulation of PTEN through its binding to CBF-1, a Notch transcription factor, and the PTEN promoter. In this study, we found that Notch3 and PTEN levels correlated with the luminal phenotype in breast cancer cell lines. Furthermore, we demonstrated that Notch3 transactivated PTEN by binding CSL-binding elements in the PTEN promoter and, at least in part, inhibiting the PTEN downstream AKT-mTOR pathway. Notably, Notch3 knockdown downregulated PTEN and promoted cell proliferation and tumorigenesis. In contrast, overexpression of the Notch3 intracellular domain upregulated PTEN and inhibited cell proliferation and tumorigenesis in vitro and in vivo. Moreover, inhibition or overexpression of PTEN partially reversed the promotion or inhibition of cell proliferation induced by Notch3 alterations. In general, Notch3 expression positively correlated with elevated expression of PTEN, ER, lower Ki-67 index, and incidence of involved node status and predicted better recurrence-free survival in breast cancer patients. Therefore, our findings demonstrate that Notch3 inhibits breast cancer proliferation and suppresses tumorigenesis by transactivating PTEN expression.
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