ArticleOncogene2015
Targeting ErbB-2 nuclear localization and function inhibits breast cancer growth and overcomes trastuzumab resistance.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- HER3 beyond the canonical paradigm: a versatile signaling hub in oncogenesis and therapeutic resistance.Journal of translational medicine · 2026Review
- The deubiquitinase USP7 stabilizes HER2 expression and promotes breast cancer progression.Neoplasia (New York, N.Y.) · 2025Article
- PAK5 promotes the trastuzumab resistance by increasing HER2 nuclear accumulation in HER2-positive breast cancer.Cell death & disease · 2025Article
- A Non-Canonical p75HER2 Signaling Pathway Underlying Trastuzumab Action and Resistance in Breast Cancer.Cells · 2024Article
- Protein tyrosine phosphatase PTPH1 potentiates receptor tyrosine kinase HER2 oncogenesis via a PDZ-coupled and phosphorylation-driven scaffold.American journal of cancer research · 2024Article
- Shc3 facilitates breast cancer drug resistance by interacting with ErbB2 to initiate ErbB2/COX2/MDR1 axis.Cancer medicine · 2023Article
- The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma.Translational oncology · 2022Review
- Halting ErbB-2 isoforms retrograde transport to the nucleus as a new theragnostic approach for triple-negative breast cancer.Cell death & disease · 2022Article
- Synthesis of Multiple Bispecific Antibody Formats with Only One Single Enzyme Based on Enhanced Trypsiligase.International journal of molecular sciences · 2022Article
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- New Advances in the Research of Resistance to Neoadjuvant Chemotherapy in Breast Cancer.International journal of molecular sciences · 2021Review
- The BA-BCS 2021: An Initial "Trial" for Integrating Basic Science and Medical Progress on Breast Cancer in a Latin-American Country.Journal of mammary gland biology and neoplasia · 2021Article
- Nuclear FGFR1 Regulates Gene Transcription and Promotes Antiestrogen Resistance in ERClinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Nuclear ErbB2 represses DEPTOR transcription to inhibit autophagy in breast cancer cells.Cell death & disease · 2021Article
- The nuclear export protein XPO1 - from biology to targeted therapy.Nature reviews. Clinical oncology · 2021Review
- Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study.Journal of experimental & clinical cancer research : CR · 2020Article
- β2-AR activation promotes cleavage and nuclear translocation of Her2 and metastatic potential of cancer cells.Cancer science · 2020Article
- Pyrotinib enhances the radiosensitivity of HER2‑overexpressing gastric and breast cancer cells.Oncology reports · 2020Article
- Rapid Target Binding and Cargo Release of Activatable Liposomes Bearing HER2 and FAP Single-Chain Antibody Fragments Reveal Potentials for Image-Guided Delivery to Tumors.Pharmaceutics · 2020Article
- Nuclear PDCD4 Expression Defines a Subset of Luminal B-Like Breast Cancers with Good Prognosis.Hormones & cancer · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Membrane overexpression of ErbB-2/HER2 receptor tyrosine kinase (membrane ErbB-2 (MErbB-2)) has a critical role in breast cancer (BC). We and others have also shown the role of nuclear ErbB-2 (NErbB-2) in BC, whose presence we identified as a poor prognostic factor in MErbB-2-positive tumors. Current anti-ErbB-2 therapies, as with the antibody trastuzumab (Ttzm), target only MErbB-2. Here, we found that blockade of NErbB-2 action abrogates growth of BC cells, sensitive and resistant to Ttzm, in a scenario in which ErbB-2, ErbB-3 and Akt are phosphorylated, and ErbB-2/ErbB-3 dimers are formed. Also, inhibition of NErbB-2 presence suppresses growth of a preclinical BC model resistant to Ttzm. We showed that at the cyclin D1 promoter, ErbB-2 assembles a transcriptional complex with Stat3 (signal transducer and activator of transcription 3) and ErbB-3, another member of the ErbB family, which reveals the first nuclear function of ErbB-2/ErbB-3 dimer. We identified NErbB-2 as the major proliferation driver in Ttzm-resistant BC, and demonstrated that Ttzm inability to disrupt the Stat3/ErbB-2/ErbB-3 complex underlies its failure to inhibit growth. Furthermore, our results in the clinic revealed that nuclear interaction between ErbB-2 and Stat3 correlates with poor overall survival in primary breast tumors. Our findings challenge the paradigm of anti-ErbB-2 drug design and highlight NErbB-2 as a novel target to overcome Ttzm resistance.
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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.