ArticleOncogene2020
SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 60 citations in OpenAlex.
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- Enhanced mitochondrial fission promotes chemosensitivity via SHP-1 activity in triple-negative breast cancer.Molecular biology reports · 2026Article
- SHP2 promotes osteosarcoma via regulating STAT3/TET3/HOXB2 signaling.Scientific reports · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Glycolytic flux sustains human Th1 identity and effector function via STAT1 glycosylation.Life science alliance · 2026Article
- Molecular Docking and Target-Specific Binding Profiles of Benzosuberane-Based Compounds.ChemMedChem · 2025Review
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model.Neuro-oncology · 2025Article
- Dynamic regulation of integrin β1 phosphorylation supports invasion of breast cancer cells.Nature cell biology · 2025Article
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain-Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors.Molecular cancer therapeutics · 2025Article
- Emerging opportunities to treat drug-resistant breast cancer: Discovery of novel small-molecule inhibitors against different targets.Frontiers in pharmacology · 2025Review
- WWP1 inhibition increases SHP2 inhibitor efficacy in colorectal cancer.NPJ precision oncology · 2024Article
- From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.Pharmaceutics · 2024Review
- Natural Product-Inspired Molecules for Covalent Inhibition of SHP2 Tyrosine Phosphatase.Tetrahedron · 2024Article
- Tyrosine phosphatase SHP2 aggravates tumor progression and glycolysis by dephosphorylating PKM2 in gastric cancer.MedComm · 2024Article
- Immunotherapeutic implications of negative regulation by protein tyrosine phosphatases in T cells: the emerging cases of PTP1B and TCPTP.Frontiers in medicine · 2024Review
- U2AF1 in various neoplastic diseases and relevant targeted therapies for malignant cancers with complex mutations (Review).Oncology reports · 2024Review
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Metastatic breast cancer (MBC) is an extremely recalcitrant disease capable of bypassing current targeted therapies via engagement of several growth promoting pathways. SH2 containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase known to facilitate growth and survival signaling downstream of numerous receptor inputs. Herein, we used inducible genetic depletion and two distinct pharmacological inhibitors to investigate the therapeutic potential of targeting SHP2 in MBC. Cells that acquired resistance to the ErbB kinase inhibitor, neratinib, displayed increased phosphorylation of SHP2 at the Y542 activation site. In addition, higher levels of SHP2 phosphorylation, but not expression, were associated with decreased survival of breast cancer patients. Pharmacological inhibition of SHP2 activity blocked ERK1/2 and AKT signaling generated from exogenous stimulation with FGF2, PDGF, and hGF and readily prevented MBC cell growth induced by these factors. SHP2 was also phosphorylated upon engagement of the extracellular matrix (ECM) via focal adhesion kinase. Consistent with the potential of SHP2-targeted compounds as therapeutic agents, the growth inhibitory property of SHP2 blockade was enhanced in ECM-rich 3D culture environments. In vivo blockade of SHP2 in the adjuvant setting decreased pulmonary metastasis and extended the survival of systemic tumor-bearing mice. Finally, inhibition of SHP2 in combination with FGFR-targeted kinase inhibitors synergistically blocked the growth of MBC cells. Overall, our findings support the conclusion that SHP2 constitutes a shared signaling node allowing MBC cells to simultaneously engage a diversity of growth and survival pathways, including those derived from the ECM.
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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 Socratic graph.