ArticleJournal of hematology & oncology2016
The D Domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells.
Article in Journal of hematology & oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
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- UM-164, a Dual Inhibitor of c-Src and p38 MAPK, Suppresses Proliferation of Glioma by Reducing YAP Activity.Cancers · 2022Article
- The Current Status of SSRP1 in Cancer: Tribulation and Road Ahead.Journal of healthcare engineering · 2022Review
- LRRC4 mediates the formation of circular RNA CD44 to inhibitGBM cell proliferation.Molecular therapy. Nucleic acids · 2021Article
- Antitumor effect of 4MU on glioblastoma cells is mediated by senescence induction and CD44, RHAMM and p-ERK modulation.Cell death discovery · 2021Article
- LINC00152 acts as a potential marker in gliomas and promotes tumor proliferation and invasion through the LINC00152/miR-107/RAB10 axis.Journal of neuro-oncology · 2021Article
- Leucine-rich repeat containing 4 act as an autophagy inhibitor that restores sensitivity of glioblastoma to temozolomide.Oncogene · 2020Article
- A novel function of IMPA2, plays a tumor-promoting role in cervical cancer.Cell death & disease · 2020Article
- LRRC4 Suppresses E-Cadherin-Dependent Collective Cell Invasion and Metastasis in Epithelial Ovarian Cancer.Frontiers in oncology · 2020Article
- LncRNA GAS5 regulates the proliferation, migration, invasion and apoptosis of brain glioma cells through targeting GSTM3 expression. The effect of LncRNA GAS5 on glioma cells.Journal of neuro-oncology · 2019Article
- miR-128-3p inhibits glioma cell proliferation and differentiation by targeting NPTX1 through IRS-1/PI3K/AKT signaling pathway.Experimental and therapeutic medicine · 2019Article
- Sirtuin 7 promotes glioma proliferation and invasion through activation of the ERK/STAT3 signaling pathway.Oncology letters · 2019Article
- Article
- Circular RNAs: Functions and Prospects in Glioma.Journal of molecular neuroscience : MN · 2019Review
- EPH receptor A2 governs a feedback loop that activates Wnt/β-catenin signaling in gastric cancer.Cell death & disease · 2018Article
- miR-519a enhances chemosensitivity and promotes autophagy in glioblastoma by targeting STAT3/Bcl2 signaling pathway.Journal of hematology & oncology · 2018Article
- Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature.Oncology letters · 2018Article
- Circular RNA hsa-circ-0012129 Promotes Cell Proliferation and Invasion in 30 Cases of Human Glioma and Human Glioma Cell Lines U373, A172, and SHG44, by Targeting MicroRNA-661 (miR-661).Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Coagulation Factor X Regulated by CASC2c Recruited Macrophages and Induced M2 Polarization in Glioblastoma Multiforme.Frontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAs a well-characterized key player in various signal transduction networks, extracellular-signal-regulated kinase (ERK1/2) has been widely implicated in the development of many malignancies. We previously found that Leucine-rich repeat containing 4 (LRRC4) was a tumor suppressor and a negative regulator of the ERK/MAPK pathway in glioma tumorigenesis. However, the precise molecular role of LRRC4 in ERK signal transmission is unclear.
methodsThe interaction between LRRC4 and ERK1/2 was assessed by co-immunoprecipitation and GST pull-down assays in vivo and in vitro. We also investigated the interaction of LRRC4 and ERK1/2 and the role of the D domain in ERK activation in glioma cells.
resultsHere, we showed that LRRC4 and ERK1/2 interact via the D domain and CD domain, respectively. Following EGF stimuli, the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and abrogates ERK1/2 activation and nuclear translocation. In glioblastoma cells, ectopic LRRC4 expression competitively inhibited the interaction of endogenous mitogen-activated protein kinase (MEK) and ERK1/2. Mutation of the D domain decreased the LRRC4-mediated inhibition of MAPK signaling and its anti-proliferation and anti-invasion roles.
conclusionsOur results demonstrated that the D domain of LRRC4 anchors ERK1/2 in the cytoplasm and competitively inhibits MEK/ERK activation in glioma cells. These findings identify a new mechanism underlying glioblastoma progression and suggest a novel therapeutic strategy by restoring the activity of LRRC4 to decrease MAPK cascade activation.
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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.