ArticleProceedings of the National Academy of Sciences of the United States of America2016
Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Chromosomal abnormalities of mesenchymal stromal cells in hematological malignancies.Oncogene · 2025Review
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- Epigenetic Profiling ofCancers · 2023Article
- Mitogen-induced defective mitosis transforms neural progenitor cells.Neuro-oncology · 2023Article
- An In Silico Study Investigating Camptothecin-Analog Interaction with Human Protein Tyrosine Phosphatase, SHP2 (PTPN11).Pharmaceuticals (Basel, Switzerland) · 2023Article
- MUC1-C is necessary for SHP2 activation and BRAF inhibitor resistance in BRAF(V600E) mutant colorectal cancer.Cancer letters · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Thoracic low grade glial neoplasm with concurrent H3 K27M and PTPN11 mutations.Acta neuropathologica communications · 2022Article
- Article
- SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia.Blood advances · 2022Article
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.Frontiers in immunology · 2022Article
- Contribution of integrin adhesion to cytokinetic abscission and genomic integrity.Frontiers in cell and developmental biology · 2022Review
- Deregulation of hsa_circ_0001971/miR-186 and hsa_circ_0001874/miR-296 signaling pathways promotes the proliferation of oral squamous carcinoma cells by synergistically activating SHP2/PLK1 signals.Scientific reports · 2021Article
- Genes causing congenital hydrocephalus: Their chromosomal characteristics of telomere proximity and DNA compositions.Experimental neurology · 2021Review
- Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms.Frontiers in cell and developmental biology · 2021Review
- A Novel Orthotopic Patient-Derived Xenograft Model of Radiation-Induced Glioma Following Medulloblastoma.Cancers · 2020Article
- The impact of RASopathy-associated mutations on CNS development in mice and humans.Molecular brain · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Gain-of-function (GOF) mutations of protein tyrosine phosphatase nonreceptor type 11 Ptpn11 (Shp2), a protein tyrosine phosphatase implicated in multiple cell signaling pathways, are associated with childhood leukemias and solid tumors. The underlying mechanisms are not fully understood. Here, we report that Ptpn11 GOF mutations disturb mitosis and cytokinesis, causing chromosomal instability and greatly increased susceptibility to DNA damage-induced malignancies. We find that Shp2 is distributed to the kinetochore, centrosome, spindle midzone, and midbody, all of which are known to play critical roles in chromosome segregation and cytokinesis. Mouse embryonic fibroblasts with Ptpn11 GOF mutations show a compromised mitotic checkpoint. Centrosome amplification and aberrant mitosis with misaligned or lagging chromosomes are significantly increased in Ptpn11-mutated mouse and patient cells. Abnormal cytokinesis is also markedly increased in these cells. Further mechanistic analyses reveal that GOF mutant Shp2 hyperactivates the Polo-like kinase 1 (Plk1) kinase by enhancing c-Src kinase-mediated tyrosine phosphorylation of Plk1. This study provides novel insights into the tumorigenesis associated with Ptpn11 GOF mutations and cautions that DNA-damaging treatments in Noonan syndrome patients with germ-line Ptpn11 GOF mutations could increase the risk of therapy-induced malignancies.
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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.