ArticleOncogene2018
Notch-1-PTEN-ERK1/2 signaling axis promotes HER2+ breast cancer cell proliferation and stem cell survival.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 108 citations in OpenAlex.
- Integrated Transcriptomic Analysis ofInternational journal of molecular sciences · 2026Article
- NOTCH2NLA gene amplification is associated with poor prognosis in breast cancer.Discover oncology · 2026Article
- Review
- 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
- Review
- Notch-1 regulates collective breast cancer cell migration by controlling intercellular junction and cytoskeletal organization.Cell proliferation · 2025Article
- Cell signaling inFrontiers in cellular and infection microbiology · 2025Review
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
- Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.Frontiers in cell and developmental biology · 2025Review
- Notch signaling in cancer: metabolic reprogramming and therapeutic implications.Frontiers in immunology · 2025Review
- Exosomal miR-182-5p from breast cancer cells reprogram tumor-associated macrophages and promote triple-negative breast cancer progression by targeting Notch1 in macrophages.Archives of medical science : AMS · 2025Article
- Review
- Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.Discover oncology · 2024Article
- Immunotherapeutic IL-6R and targeting the MCT-1/IL-6/CXCL7/PD-L1 circuit prevent relapse and metastasis of triple-negative breast cancer.Theranostics · 2024Article
- Resistance mechanisms and prospects of trastuzumab.Frontiers in oncology · 2024Review
- Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.Advances in experimental medicine and biology · 2024Review
- The application of nanoparticles in theranostic systems targeting breast cancer stem cells: current progress and future challenges.Stem cell research & therapy · 2023Review
- Intervening in hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p for tumor microenvironment regulation and cancer therapy.Journal of nanobiotechnology · 2023Article
- Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer.Nature communications · 2023Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
Trastuzumab targets the HER2 receptor on breast cancer cells to attenuate HER2-driven tumor growth. However, resistance to trastuzumab-based therapy remains a major clinical problem for women with HER2+ breast cancer. Breast cancer stem cells (BCSCs) are suggested to be responsible for drug resistance and tumor recurrence. Notch signaling has been shown to promote BCSC survival and self-renewal. Trastuzumab-resistant cells have increased Notch-1 expression. Notch signaling drives cell proliferation in vitro and is required for tumor recurrence in vivo. We demonstrate herein a mechanism by which Notch-1 is required for trastuzumab resistance by repressing PTEN expression to contribute to activation of ERK1/2 signaling. Furthermore, Notch-1-mediated inhibition of PTEN is necessary for BCSC survival in vitro and in vivo. Inhibition of MEK1/2-ERK1/2 signaling in trastuzumab-resistant breast cancer cells mimics effects of Notch-1 knockdown on bulk cell proliferation and BCSC survival. These findings suggest that Notch-1 contributes to trastuzumab resistance by repressing PTEN and this may lead to hyperactivation of ERK1/2 signaling. Furthermore, high Notch-1 and low PTEN mRNA expression may predict poorer overall survival in women with breast cancer. Notch-1 protein expression predicts poorer survival in women with HER2+ breast cancer. These results support a potential future clinical trial combining anti-Notch-1 and anti-MEK/ERK therapy for trastuzumab-resistant breast cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.