ArticleScientific reports2016
Disrupting VEGF-A paracrine and autocrine loops by targeting SHP-1 suppresses triple negative breast cancer metastasis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 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
- Gene expression alterations predict the pathological complete response in triple-negative breast cancer exploratory analysis of the NACATRINE trial.Scientific reports · 2023Trial
- Endogenous promoter G-quadruplexes scaffold apurinic/apyrimidinic endonuclease (APE1) to drive gene expression.Nucleic acids research · 2026Article
- Network-based exploration of 4-(phenylsulfonyl)morpholine molecules for metastatic triple-negative breast cancer suppression.PLoS computational biology · 2026Article
- Tumor-derived small extracellular vesicles loaded with functionally active miR-34a mimic can modify the anti-tumor response in 4T1 breast cancer animal model.Cancer cell international · 2025Article
- Research progress of SHP-1 agonists as a strategy for tumor therapy.Molecular diversity · 2025Review
- Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- The potential of lenvatinib in breast cancer therapy.Medical oncology (Northwood, London, England) · 2024Review
- Role of Protein Phosphatases in Tumor Angiogenesis: Assessing PP1, PP2A, PP2B and PTPs Activity.International journal of molecular sciences · 2024Review
- Genomic characterization reveals distinct mutational landscapes and therapeutic implications between different molecular subtypes of triple-negative breast cancer.Scientific reports · 2024Article
- TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.Cell death & disease · 2024Article
- Potential therapeutic targets of the JAK2/STAT3 signaling pathway in triple-negative breast cancer.Frontiers in oncology · 2024Review
- Reprogramming of VEGF-mediated extracellular matrix changes through autocrine signaling.Cancer biology & therapy · 2023Article
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
- MOBILE pipeline enables identification of context-specific networks and regulatory mechanisms.Nature communications · 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
- Bispecific antibodies revolutionizing breast cancer treatment: a comprehensive overview.Frontiers in immunology · 2023Review
- Synergistic Anti-Angiogenic Effect of Combined VEGFR Kinase Inhibitors, Lenvatinib, and Regorafenib: A Therapeutic Potential for Breast Cancer.International journal of molecular sciences · 2022Article
- Immunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy.Frontiers in immunology · 2022Review
- Targeting microRNAs with thymoquinone: a new approach for cancer therapy.Cellular & molecular biology letters · 2021Review
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with triple-negative breast cancer (TNBC) had an increased likelihood of distant recurrence and death, as compared with those with non-TNBC subtype. Regorafenib is a multi-receptor tyrosine kinase (RTK) inhibitor targeting oncogenesis and has been approved for metastatic colorectal cancer and advanced gastrointestinal stromal tumor. Recent studies suggest regorafenib acts as a SHP-1 phosphatase agonist. Here, we investigated the potential of regorafenib to suppress metastasis of TNBC cells through targeting SHP-1/p-STAT3/VEGF-A axis. We found a significant correlation between cancer cell migration and SHP-1/p-STAT3/VEGF-A expression in human TNBC cells. Clinically, high VEGF-A expression is associated with worse disease-free and distant metastasis-free survival. Regorafenib induced significant anti-migratory effects, in association with downregulation of p-STAT3 and VEGF-A. To exclude the role of RTK inhibition in regorafenib-induced anti-metastasis, we synthesized a regorafenib derivative, SC-78, that had minimal effect on VEGFR2 and PDGFR kinase inhibition, while having more potent effects on SHP-1 activation. SC-78 demonstrated superior in vitro and in vivo anti-migration to regorafenib. Furthermore, VEGF-A dependent autocrine/paracrine loops were disrupted by regorafenib and SC-78. This study implies that SHP-1/p-STAT3/VEGF-A axis is a potential therapeutic target for metastatic TNBC, and the more potent SC-78 may be a promising lead for suppressing metastasis of TNBC.
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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.