ArticleOncoTargets and therapy2019
Gain-Of-Function E76K-Mutant SHP2 Promotes Cell Proliferation, Metastasis, And Tumor Growth In Glioblastoma Through Activation Of The ERK/CREB Pathway.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed, 15 citations in OpenAlex.
- ZBTB20 suppresses tumor growth in glioblastoma through activating the TET1/FAS/caspase‑3 pathway.Oncology letters · 2024Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- A novel stop-gain pathogenic variant in FLT4 and a nonsynonymous pathogenic variant in PTPN11 associated with congenital heart defects.European journal of medical research · 2022Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Dissecting protein tyrosine phosphatase signaling by engineered chemogenetic control of its activity.The Journal of cell biology · 2022Article
- PTPN11 Gene Mutations and Its Association with the Risk of Congenital Heart Disease.Disease markers · 2022Article
- Genomic Analysis of Tumors from Patients with Glioblastoma with Long-Term Response to Afatinib.OncoTargets and therapy · 2022Article
- Exploring the dynamic mechanism of allosteric drug SHP099 inhibiting SHP2Molecular diversity · 2021Article
- Inhibitory role of circRNA_100395 in the proliferation and metastasis of prostate cancer cells.The Journal of international medical research · 2021Article
- Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe aim of this study was to investigate the effects of gain-of-function (GOF) E76K-mutant Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) on the biological behaviors of glioblastoma (GBM) cells, and explore the molecular mechanisms of GBM progression.
methodsFirstly, a negative control vector and vectors overexpressing SHP2 and E76K-mutant SHP2 were transduced into GBM cells (U87 and A172) using a lentivirus. The effect of GOF-mutant SHP2 on proliferation was measured using the MTT assay, flow cytometry, colony formation assay, and soft agar assay. Moreover, the migration and invasion of GBM cells were determined through the transwell assay. Related proteins of the extracellular signal-regulated kinase/cAMP response element binding protein (ERK/CREB) pathway were detected by Western blotting analysis. A xenograft model was established to confirm the tumor-promoting effect of GOF-mutant SHP2 in vivo. Finally, ERK was inhibited using a mitogen-activated protein kinase/ERK kinase inhibitor (U0126) to further explore the molecular mechanism of GOF-mutant SHP2 affecting GBM cells.
resultsAfter transduction, the expression of SHP2 in the SHP2-mutant and SHP2-overexpression groups was higher than that observed in the control and normal groups. Our data indicated that GOF-mutant SHP2 enhanced the abilities of GBM cells for proliferation, migration, and invasion in vitro, and promoted tumor growth in vivo. Mechanistically, the ERK/CREB pathway was activated, and the levels of relevant proteins were increased in the SHP2-mutant group. Furthermore, following inhibition of ERK in the GOF-SHP2 mutant group, the activation of CREB was also depressed, and the malignant biological behaviors were weakened accordingly.
conclusionThe GOF-mutant SHP2 promoted GBM cell proliferation, metastasis, and tumor growth through the ERK/CREB pathway, providing a promising target for the treatment of GBM.
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.