ArticlePloS one2016
RalGPS2 Is Essential for Survival and Cell Cycle Progression of Lung Cancer Cells Independently of Its Established Substrates Ral GTPases.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 20 citations in OpenAlex.
- Single-cell catalogue of immune cells from Japanese individuals.Communications biology · 2026Article
- Integrative multi-omics analysis identifies methylation-associated lncRNAs FAM83A-AS2 and AC012213.1 as candidate prognostic markers in lung adenocarcinoma.Bioinformatics advances · 2026Article
- Unveiling critical genes and molecular subtypes in ovarian cancer: insights into tumor immunity and carbohydrate-lipid metabolism.Translational cancer research · 2025Article
- [RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assemblyNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Review
- A general calculus of fitness landscapes finds genes under selection in cancers.Genome research · 2022Article
- RGL2 Drives the Metastatic Progression of Colorectal Cancer via Preventing the Protein Degradation of β-Catenin and KRAS.Cancers · 2021Article
- Comparative Analysis of Multiple Neurodegenerative Diseases Based on Advanced Epigenetic Aging Brain.Frontiers in genetics · 2021Article
- Integrative Analysis of Three Novel Competing Endogenous RNA Biomarkers with a Prognostic Value in Lung Adenocarcinoma.BioMed research international · 2020Article
- Localization of RalB signaling at endomembrane compartments and its modulation by autophagy.Scientific reports · 2019Article
- Integrative Analysis of Somatic Mutations in Non-coding Regions Altering RNA Secondary Structures in Cancer Genomes.Scientific reports · 2019Article
- Dynamic expression and functional analysis of circRNA in granulosa cells during follicular development in chicken.BMC genomics · 2019Article
- Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering.Scientific reports · 2018Article
- Identification of HIF-2α-regulated genes that play a role in human microvascular endothelial sprouting during prolonged hypoxia in vitro.Angiogenesis · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human genome contains six genes coding for proteins validated in vitro as specific activators of the small GTPases "Ras-related protein Ral-A" and "Ras-related protein Ral-B", generically named Ral-guanine nucleotide exchange factors (RalGEF). Ral proteins are important contributors to Ras oncogenic signaling, and RAS oncogenes are important in human Non-Small Cell Lung Carcinoma (NSCLC). Therefore in this work, RalGEF contribution to oncogenic and non-oncogenic features of human NSCLC cell lines, as anchorage-dependent and independent growth, cell survival, and proliferation, was investigated. Among all human RalGEF, silencing of RGL1 and RALGPS1 had no detectable effect. However, silencing of either RGL2, RGL3, RALGDS or, to a larger extent, RALGPS2 inhibited cell population growth in anchorage dependent and independent conditions (up to 90 and 80%, respectively). RALGPS2 silencing also caused an increase in the number of apoptotic cells, up to 45% of the cell population in transformed bronchial BZR cells. In H1299 and A549, two NSCLC cell lines, RALGPS2 silencing caused an arrest of cells in the G0/G1-phase of cell cycle. Furthermore, it was associated with the modulation of important cell cycle regulators: the E3 Ubiquitin Protein Ligase S-phase kinase-associated protein 2 (Skp2) was strongly down-regulated (both at mRNA and protein levels), and its targets, the cell cycle inhibitors p27 and p21, were up-regulated. These molecular effects were not mimicked by silencing RALA, RALB, or both. However, RALB silencing caused a modest inhibition of cell cycle progression, which in H1299 cells was associated with Cyclin D1 regulation. In conclusion, RALGPS2 is implicated in the control of cell cycle progression and survival in the in vitro growth of NSCLC cell lines. This function is largely independent of Ral GTPases and associated with modulation of Skp2, p27 and p21 cell cycle regulators.
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