ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
PKCα Attenuates Jagged-1-Mediated Notch Signaling in ErbB-2-Positive Breast Cancer to Reverse Trastuzumab Resistance.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- MarkerPredict: predicting clinically relevant predictive biomarkers with machine learning.NPJ systems biology and applications · 2025Article
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Advances in Molecular Diagnostics and Targeted Therapeutic Approaches in HER-2 Positive Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Review
- Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.Frontiers in cell and developmental biology · 2025Review
- Biofunctional study on chemoresistance in esophageal squamous carcinoma cells induced by missense mutation ofJournal of thoracic disease · 2024Article
- Identification of a Notch transcriptomic signature for breast cancer.Breast cancer research : BCR · 2024Article
- Advances in understanding the role and mechanisms of tumor stem cells in HER2-positive breast cancer treatment resistance (Review).International journal of oncology · 2023Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- In Silico Identification of Genes Associated with Breast Cancer Progression and Prognosis and Novel Therapeutic Targets.Biomedicines · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Galectin-3 enhances trastuzumab resistance by regulating cancer malignancy and stemness in HER2-positive breast cancer cells.Thoracic cancer · 2022Article
- Roles of Notch Signaling in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- Targeting Notch in oncology: the path forward.Nature reviews. Drug discovery · 2021Review
- E3 Ubiquitin Ligase in Anticancer Drugdsla Resistance: Recent Advances and Future Potential.Frontiers in pharmacology · 2021Review
- Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.Frontiers in endocrinology · 2021Article
- Notch Signalling in Breast Development and Cancer.Frontiers in cell and developmental biology · 2021Review
- Review
- Inhibition of HER2 Increases JAGGED1-dependent Breast Cancer Stem Cells: Role for Membrane JAGGED1.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeBreast cancer is the second leading cause of cancer mortality among women worldwide. The major problem with current treatments is tumor resistance, recurrence, and disease progression. ErbB-2-positive breast tumors are aggressive and frequently become resistant to trastuzumab or lapatinib. We showed previously that Notch-1 is required for trastuzumab resistance in ErbB-2-positive breast cancer. EXPERIMENTAL
designHere, we sought to elucidate mechanisms by which ErbB-2 attenuates Notch signaling and how this is reversed by trastuzumab or lapatinib.
resultsThe current study elucidates a novel Notch inhibitory mechanism by which PKCα downstream of ErbB-2 (i) restricts the availability of Jagged-1 at the cell surface to transactivate Notch, (ii) restricts the critical interaction between Jagged-1 and Mindbomb-1, an E3 ligase that is required for Jagged-1 ubiquitinylation and subsequent Notch activation, (iii) reverses trastuzumab resistance in vivo, and (iv) predicts better outcome in women with ErbB-2-positive breast cancer.
conclusionsThe clinical impact of these studies is PKCα is potentially a good prognostic marker for low Notch activity and increased trastuzumab sensitivity in ErbB-2-positive breast cancer. Moreover, women with ErbB-2-positive breast tumors expressing high Notch activation and low PKCα expression could be the best candidates for anti-Notch therapy.
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Registered trials
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