ArticleThe EMBO journal2015
Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- SHP2 negatively regulates TGF-β signaling by destabilizing the TGF-β type I receptor.Cell communication and signaling : CCS · 2026Article
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Inhibition of protein kinase C delta leads to cellular senescence to induce anti-tumor effects in colorectal cancer.Cancer science · 2023Article
- New frontiers in immune checkpoint B7-H3 (CD276) research and drug development.Molecular cancer · 2023Review
- A Formylglycine-Peptide for the Site-Directed Identification of Phosphotyrosine-Mimetic Fragments.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway.Cell death & disease · 2021Article
- Senescence under appraisal: hopes and challenges revisited.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer.Oncogene · 2020Article
- Review
- B-Raf deficiency impairs tumor initiation and progression in a murine breast cancer model.Oncogene · 2019Article
- SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling.Frontiers in immunology · 2019Review
- Two-Step Senescence-Focused Cancer Therapies.Trends in cell biology · 2018Review
- SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo.Nature medicine · 2018Article
- Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase.Nature medicine · 2018Article
- Frequent overexpression of AMAP1, an Arf6 effector in cell invasion, is characteristic of the MMTV-PyMT rather than the MMTV-Neu human breast cancer model.Cell communication and signaling : CCS · 2018Article
- Article
- Snail1-dependent p53 repression regulates expansion and activity of tumour-initiating cells in breast cancer.Nature cell biology · 2016Article
- Polyphenols as Modulator of Oxidative Stress in Cancer Disease: New Therapeutic Strategies.Oxidative medicine and cellular longevity · 2016Review
Corrections and comments
- Commented on by
- Erratum issuedShp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice.2015 · Rademann, Jörg [added]
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we have used techniques from cell biology, biochemistry, and genetics to investigate the role of the tyrosine phosphatase Shp2 in tumor cells of MMTV-PyMT mouse mammary glands. Genetic ablation or pharmacological inhibition of Shp2 induces senescence, as determined by the activation of senescence-associated β-gal (SA-β-gal), cyclin-dependent kinase inhibitor 1B (p27), p53, and histone 3 trimethylated lysine 9 (H3K9me3). Senescence induction leads to the inhibition of self-renewal of tumor cells and blockage of tumor formation and growth. A signaling cascade was identified that acts downstream of Shp2 to counter senescence: Src, focal adhesion kinase, and Map kinase inhibit senescence by activating the expression of S-phase kinase-associated protein 2 (Skp2), Aurora kinase A (Aurka), and the Notch ligand Delta-like 1 (Dll1), which block p27 and p53. Remarkably, the expression of Shp2 and of selected target genes predicts human breast cancer outcome. We conclude that therapies, which rely on senescence induction by inhibiting Shp2 or controlling its target gene products, may be useful in blocking 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.