ArticleJournal of molecular medicine (Berlin, Germany)2017
Sequential combination of docetaxel with a SHP-1 agonist enhanced suppression of p-STAT3 signaling and apoptosis in triple negative breast cancer cells.
Article in Journal of molecular medicine (Berlin, Germany), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019Pooled it
- Research progress of SHP-1 agonists as a strategy for tumor therapy.Molecular diversity · 2025Review
- Multi-omic analyses reveal PTPN6's impact on tumor immunity across various cancers.Scientific reports · 2025Article
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- 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
- Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.Journal of hematology & oncology · 2022Review
- JAK-STAT core cancer pathway: An integrative cancer interactome analysis.Journal of cellular and molecular medicine · 2022Review
- SH003 and Docetaxel Show Synergistic Anticancer Effects by Inhibiting EGFR Activation in Triple-Negative Breast Cancer.BioMed research international · 2022Article
- Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy.Frontiers in oncology · 2022Review
- Distinct Somatic Alteration Features Identified by Gene Panel Sequencing in Korean Triple-Negative Breast Cancer with High Ki67 Expression.Diagnostics (Basel, Switzerland) · 2021Article
- Novel treatment strategies for patients with HER2-positive breast cancer who do not benefit from current targeted therapy drugs.Experimental and therapeutic medicine · 2018Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Triple negative breast cancer (TNBC) is an aggressive cancer for which prognosis remains poor. Combination therapy is a promising strategy for enhancing treatment efficacy. Blockade of STAT3 signaling may enhance the response of cancer cells to conventional chemotherapeutic agents. Here we used a SHP-1 agonist SC-43 to dephosphorylate STAT3 thereby suppressing oncogenic STAT3 signaling and tested it in combination with docetaxel in TNBC cells. We first analyzed messenger RNA (mRNA) expression of SHP-1 gene (PTPN6) in a public TNBC dataset (TCGA) and found that higher SHP-1 mRNA expression is associated with better overall survival in TNBC patients. Sequential combination of docetaxel and SC-43 in vitro showed enhanced anti-proliferation and apoptosis associated with decreased p-STAT3 and decreased STAT3-downstream effector cyclin D1 in the TNBC cell lines MDA-MB-231, MDA-MB-468, and HCC-1937. Ectopic expression of STAT3 reduced the increased cytotoxicity induced by the combination therapy. In addition, this sequential combination showed enhanced SHP-1 activity compared to SC-43 alone. Furthermore, the combination treatment-induced apoptosis was attenuated by small interfering RNA (siRNA) against SHP-1 or by ectopic expression of SHP-1 mutants that caused SC-43 to lose its SHP-1 agonist capability. Moreover, combination of docetaxel and SC-43 showed enhanced tumor growth inhibition compared to single-agent therapy in mice bearing MDA-MB-231 tumor xenografts. Our results suggest that the novel SHP-1 agonist SC-43 enhanced docetaxel-induced cytotoxicity by SHP-1 dependent STAT3 inhibition in human triple negative breast cancer cells. TNBC patients with high SHP-1 expressions show better survival. Docetaxel combined with SC-43 enhances cell apoptosis and reduces p-STAT3. SHP-1 inhibition reduces the enhanced effect of docetaxel-SC-43 combination. Docetaxel-SC-43 combination suppresses xenograft tumor growth and reduces p-STAT3. KEY MESSAGES: TNBC patients with high SHP-1 expressions show better survival. Docetaxel combined with SC-43 enhances cell apoptosis and reduces p-STAT3. SHP-1 inhibition reduces the enhanced effect of docetaxel-SC-43 combination. Docetaxel-SC-43 combination suppresses xenograft tumor growth and reduces p-STAT3.
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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.