ArticleJournal of experimental & clinical cancer research : CR2019
NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- NDR2 regulates non-small cell lung cancer cell migration under starvation by supporting autophagosome biogenesis through LC3 and ATG9A regulation.Cell death discovery · 2025Article
- NDR1/2 kinases regulate cell polarization and cell motility through Cdc42 GTPase and Pard3 signaling in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- YAP/TEAD involvement in resistance to paclitaxel chemotherapy in lung cancer.Molecular and cellular biochemistry · 2025Article
- Article
- Targeting the Hippo pathway to prevent radioresistance brain metastases from the lung (Review).International journal of oncology · 2024Review
- The NDR family of kinases: essential regulators of aging.Frontiers in molecular neuroscience · 2024Review
- Hypoxia-induced activation of NDR2 underlies brain metastases from Non-Small Cell Lung Cancer.Cell death & disease · 2023Article
- Article
- The Role of Mammalian STK38 in DNA Damage Response and Targeting for Radio-Sensitization.Cancers · 2023Review
- Molecular Alterations in Malignant Pleural Mesothelioma: A Hope for Effective Treatment by Targeting YAP.Targeted oncology · 2022Review
- Evaluation of Methylation Panel in the Promoter Region ofArchives of Razi Institute · 2022Article
- Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease.Cells · 2022Article
- The Diagnostic Potential ofFrontiers in oncology · 2022Article
- Review
- Centrosome, the Newly Identified Passenger through Tunneling Nanotubes, Increases Binucleation and Proliferation Marker in Receiving Cells.International journal of molecular sciences · 2021Article
- Resistance to Targeted Therapy and RASSF1A Loss in Melanoma: What Are We Missing?International journal of molecular sciences · 2021Review
- The STK38-XPO1 axis, a new actor in physiology and cancer.Cellular and molecular life sciences : CMLS · 2021Review
- MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression.Disease markers · 2021Article
- RASSF1A inhibits PDGFB-driven malignant phenotypes of nasopharyngeal carcinoma cells in a YAP1-dependent manner.Cell death & disease · 2020Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundRASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown.
methodsNDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID-/- Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC).
resultsWe demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC.
conclusionTo summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects.
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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.