ArticleThe Journal of biological chemistry2009
Molecular mechanism for SHP2 in promoting HER2-induced signaling and transformation.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Targeting SHP2 with an Active Site Inhibitor Blocks Signaling and Breast Cancer Cell Phenotypes.ACS bio & med chem Au · 2023Article
- Article
- Article
- Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors.RSC medicinal chemistry · 2022Review
- Strategies to overcome drug resistance using SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Review
- SHP2 Potentiates the Oncogenic Activity of β-Catenin to Promote Triple-Negative Breast Cancer.Molecular cancer research : MCR · 2021Article
- Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib.Cancer research · 2020Article
- Review
- Novel Small-Molecule Inhibitor for the Oncogenic Tyrosine Phosphatase SHP2 with Anti-Breast Cancer Cell Effects.ACS omega · 2020Article
- A specific amino acid context in EGFR and HER2 phosphorylation sites enables selective binding to the active site of Src homology phosphatase 2 (SHP2).The Journal of biological chemistry · 2020Article
- Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational In Vitro-In Silico Model.Oxidative medicine and cellular longevity · 2020Article
- Article
- Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.Oncogene · 2019Article
- "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.Frontiers in oncology · 2018Review
- Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated increase in CA916798.Oncotarget · 2017Article
- The Shp2-induced epithelial disorganization defect is reversed by HDAC6 inhibition independent of Cdc42.Nature communications · 2016Article
- SHP2 acts both upstream and downstream of multiple receptor tyrosine kinases to promote basal-like and triple-negative breast cancer.Breast cancer research : BCR · 2016Article
- Functions of Shp2 in cancer.Journal of cellular and molecular medicine · 2015Review
- Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway.BMC cancer · 2015Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Src homology phosphotyrosyl phosphatase 2 (SHP2) plays a positive role in HER2-induced signaling and transformation, but its mechanism of action is poorly understood. Given the significance of HER2 in breast cancer, defining a mechanism for SHP2 in the HER2 signaling pathway is of paramount importance. In the current report we show that SHP2 positively modulates the Ras-extracellular signal-regulated kinase 1 and 2 and the phospoinositide-3-kinase-Akt pathways downstream of HER2 by increasing the half-life the activated form of Ras. This is accomplished by dephosphorylating an autophosphorylation site on HER2 that serves as a docking platform for the SH2 domains of the Ras GTPase-activating protein (RasGAP). The net effect is an increase in the intensity and duration of GTP-Ras levels with the overall impact of enhanced HER2 signaling and cell transformation. In conformity to these findings, the HER2 mutant that lacks the SHP2 target site exhibits an enhanced signaling and cell transformation potential. Therefore, SHP2 promotes HER2-induced signaling and transformation at least in part by dephosphorylating a negative regulatory autophosphorylation site. These results suggest that SHP2 might serve as a therapeutic target against breast cancer and other cancers characterized by HER2 overexpression.
Indexed as
Identifiers
What OpenQuestion holds
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.