ArticleCancers2020
Specific Roles of HSP27 S15 Phosphorylation Augmenting the Nuclear Function of HER2 to Promote Trastuzumab Resistance.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 25 citations in OpenAlex.
- Discovery of a Small-Molecule Inhibitor Targeting the ELF3-HSP27 Interaction to Suppress Breast Cancer Progression.Pharmaceuticals (Basel, Switzerland) · 2026Article
- AXL inhibition improves the therapeutic efficacy of trastuzumab in high-risk endometrial cancer.Gynecologic oncology · 2026Article
- Dually Decorated Palmitate-Containing Lipid Nanoparticles for the Targeted Delivery of siRNAs against HER2 and Hsp27 in HER2Journal of medicinal chemistry · 2025Article
- 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
- Two sides of the same coin: heat shock proteins as biomarkers and therapeutic targets for some complex diseases.Frontiers in molecular biosciences · 2025Review
- [Effect of phosphorylated HSP27 on the proliferation and metastasis of nasopharyngeal carcinoma and its mechanism].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2024Article
- Review
- Heat Shock Proteins and Breast Cancer.International journal of molecular sciences · 2024Review
- Small molecule heat shock protein 27 inhibitor J2 decreases ovarian cancer cell proliferation via induction of apoptotic pathways.Medical oncology (Northwood, London, England) · 2023Article
- Interrupting specific hydrogen bonds between ELF3 and MED23 as an alternative drug resistance-free strategy for HER2-overexpressing cancers.Journal of advanced research · 2023Article
- Mechanistic insights into heat shock protein 27, a potential therapeutic target for cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Activation of the HSP27-AKT axis contributes to gefitinib resistance in non-small cell lung cancer cells independent of EGFR mutations.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Article
- The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90.International journal of molecular sciences · 2022Review
- The Role of Hsp27 in Chemotherapy Resistance.Biomedicines · 2022Review
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- Cluster analyses of the TCGA and a TMA dataset using the coexpression of HSP27 and CRYAB improves alignment with clinical-pathological parameters of breast cancer and suggests different epichaperome influences for each sHSP.Cell stress & chaperones · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Trastuzumab (TZMB) is widely used as first line therapy for breast cancer (BC) patients overexpressing human epidermal growth factor receptor 2 (HER2). Despite its clinical benefits, many patients suffer from primary or secondary resistance to this drug within one year. As diverse molecular mechanisms occur contemporaneously during the resistance development, we focused on elucidating the role of heat shock protein 27 (HSP27) in TZMB-resistance, as this protein simultaneously regulates the function of diverse client molecules that are involved in the resistance mechanism. By extensively utilizing TZMB-refractory breast cancer cell lines transduced with diverse phosphovariants of HSP27, our study newly revealed that specific phosphorylation of HSP27 at S15 promoted its S78 phosphorylation and served as key mediator to promote direct interactions that increase the stability of HER2 and protein kinase B (AKT). This phosphorylation promoted nuclear translocation of HER2, enhancing the distinct nuclear function of HER2 that promoted AKT activation and cyclin D1 expression. Co-administration of TZMB and a functional inhibitor of HSP27, J2, significantly reduced the S15/78 phosphorylation of HSP27, which downregulated HER2 and its downstream signals, sensitizing TZMB-refractory cell, and JIMT1-xenograft mouse models to TZMB. Collectively, p-HSP27
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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.