ArticleNature medicine2012
Tyrosine phosphatase SHP2 promotes breast cancer progression and maintains tumor-initiating cells via activation of key transcription factors and a positive feedback signaling loop.
Article in Nature medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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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
160 citing papers in PubMed, 266 citations in OpenAlex.
- Enhanced mitochondrial fission promotes chemosensitivity via SHP-1 activity in triple-negative breast cancer.Molecular biology reports · 2026Article
- Discovery of a Dual IDO1/TDO Inhibitor That Modulates Enzymatic Activity and IDO1/SHP-2 Signaling.Journal of medicinal chemistry · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- AI-Guided Discovery of Oncogenic Signaling Crosstalk in Tumor Progression and Drug Resistance.Oncology research · 2026Review
- SHP2 inhibition reduces somatotroph tumor growth in a pre-clinical model.Neuro-oncology · 2025Article
- Deep mutational scanning of the multi-domain phosphatase SHP2 reveals mechanisms of regulation and pathogenicity.Nature communications · 2025Article
- Computational Elucidation of a Monobody Targeting the Phosphatase Domain of SHP2.Biomolecules · 2025Article
- SHP2 is essential for the progesterone-promoted proliferation and migration in breast cancer cell lines.Frontiers in endocrinology · 2025Article
- The Expression of PDL-1 and PD1 in the Microenvironment of Oral Squamous Cell Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- From Tyrosine Kinases to Tyrosine Phosphatases: New Therapeutic Targets in Cancers and Beyond.Pharmaceutics · 2024Review
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- RETRACTED: Protein Tyrosine Phosphatase Non-Receptor 11 (International journal of molecular sciences · 2023Article
- PI3K inhibition circumvents resistance to SHP2 blockade in metastatic triple-negative breast cancer.Journal of mammary gland biology and neoplasia · 2023Article
- A Comprehensive Analysis Revealing FBXW9 as a Potential Prognostic and Immunological Biomarker in Breast Cancer.International journal of molecular sciences · 2023Article
- An Integrated Proteomic Strategy to Identify SHP2 Substrates.Journal of proteome research · 2022Article
- Tumor Cell-Autonomous SHP2 Contributes to Immune Suppression in Metastatic Breast Cancer.Cancer research communications · 2022Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
100 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 8 institutions in 3 countries.
Funding
Abstract
New cancer therapies are likely to arise from an in-depth understanding of the signaling networks influencing tumor initiation, progression and metastasis. We show a fundamental role for Src-homology 2 domain-containing phosphatase 2 (SHP2) in these processes in human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers. Knockdown of SHP2 eradicated breast tumor-initiating cells in xenograft models, and SHP2 depletion also prevented invasion in three-dimensional cultures and in a transductal invasion assay in vivo. Notably, SHP2 knockdown in established breast tumors blocked their growth and reduced metastasis. Mechanistically, SHP2 activated stemness-associated transcription factors, including v-myc myelocytomatosis viral oncogene homolog (c-Myc) and zinc finger E-box binding homeobox 1 (ZEB1), which resulted in the repression of let-7 microRNA and the expression of a set of 'SHP2 signature' genes. We found these genes to be simultaneously activated in a large subset of human primary breast tumors that are associated with invasive behavior and poor prognosis. These results provide new insights into the signaling cascades influencing tumor-initiating cells as well as a rationale for targeting SHP2 in breast cancer.
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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.