ArticleExperimental & molecular medicine2017
The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells.
Article in Experimental & molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019Pooled it
- Shp1 phosphatase regulates CXCR2 protein stability and IL8-mediated invasiveness in breast cancer.Cell death & disease · 2026Article
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- Nintedanib enhances tumor cell radiosensitivity by promoting ferroptosis and modulating the ATF4/SLC7A11/GSH axis.Cancer biology & medicine · 2025Article
- Research progress of SHP-1 agonists as a strategy for tumor therapy.Molecular diversity · 2025Review
- Targeting kinases that regulate programmed cell death: a new therapeutic strategy for breast cancer.Journal of translational medicine · 2025Review
- Multi-omic analyses reveal PTPN6's impact on tumor immunity across various cancers.Scientific reports · 2025Article
- Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.Antioxidants (Basel, Switzerland) · 2024Article
- Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF).Expert review of clinical pharmacology · 2024Review
- ETHE1 dampens colorectal cancer angiogenesis by promoting TC45 Dephosphorylation of STAT3 to inhibit VEGF-A expression.Cell death & disease · 2024Article
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Prognostic Markers in Tyrosine Kinases Specific to Basal-like 2 Subtype of Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.International journal of molecular sciences · 2023Review
- SH2 Domain-Containing Phosphatase-SHP2 Attenuates Fibrotic Responses through Negative Regulation of Mitochondrial Metabolism in Lung Fibroblasts.Diagnostics (Basel, Switzerland) · 2023Article
- Synthesis and Biological Evaluation of 3-Amino-4,4-Dimethyl Lithocholic Acid Derivatives as Novel, Selective, and Cellularly Active Allosteric SHP1 Activators.Molecules (Basel, Switzerland) · 2023Article
- Transcriptomic Analysis of Subtype-Specific Tyrosine Kinases as Triple Negative Breast Cancer Biomarkers.Cancers · 2023Article
- Nintedanib induces senolytic effect via STAT3 inhibition.Cell death & disease · 2022Article
- Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma.Molecular medicine (Cambridge, Mass.) · 2022Article
- Targeted dual inhibition of c-Met/VEGFR2 signalling by foretinib improves antitumour effects of nanoparticle paclitaxel in gastric cancer models.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Indexed as
Identifiers
What OpenQuestion holds
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.