ArticleThe Journal of biological chemistry2013
Tumor cell migration and invasion are enhanced by depletion of Rap1 GTPase-activating protein (Rap1GAP).
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Modulation of the cytoskeleton for cancer therapy.Frontiers in cell and developmental biology · 2025Article
- Chaihu Longgu Muli Decoction inhibits chronic stress-induced lung cancer epithelial-mesenchymal transition process by suppressing Rap1/ERK signal pathway.Frontiers in pharmacology · 2025Article
- Microtubule regulation in cancer cells.Frontiers in cell and developmental biology · 2025Article
- Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.Archives of toxicology · 2024Article
- CRISPR/Cas9 mediated Y-chromosome elimination affects human cells transcriptome.Cell & bioscience · 2024Article
- TGF-β1-induced RAP2 regulates invasion in pancreatic cancer.Acta biochimica et biophysica Sinica · 2022Article
- Simulated Microgravity Increases the Permeability of HUVEC Monolayer through Up-Regulation of Rap1GAP and Decreased Rap2 Activation.International journal of molecular sciences · 2022Article
- Mex3a promotes oncogenesis through the RAP1/MAPK signaling pathway in colorectal cancer and is inhibited by hsa-miR-6887-3p.Cancer communications (London, England) · 2021Article
- Novel compound cedrelone inhibits hepatocellular carcinoma progression via PBLD and Ras/Rap1.Experimental and therapeutic medicine · 2019Article
- A unique role for clathrin light chain A in cell spreading and migration.Journal of cell science · 2019Article
- Tissue specific human fibroblast differential expression based on RNAsequencing analysis.BMC genomics · 2019Article
- Methylation level of Rap1GAP and the clinical significance in MDS.Oncology letters · 2018Article
- Downregulation of Rap1Gap: A Switch from DCIS to Invasive Breast Carcinoma via ERK/MAPK Activation.Neoplasia (New York, N.Y.) · 2018Article
- The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression.Oncology letters · 2018Article
- Roles of Rap1 signaling in tumor cell migration and invasion.Cancer biology & medicine · 2017Article
- Low expression of Rap1GAP is associated with epithelial-mesenchymal transition (EMT) and poor prognosis in gastric cancer.Oncotarget · 2017Article
- Structure, functional regulation and signaling properties of Rap2B.Oncology letters · 2016Article
- The alternative splicing factor Nova2 regulates vascular development and lumen formation.Nature communications · 2015Article
- A novel 2.5D culture platform to investigate the role of stiffness gradients on adhesion-independent cell migration.PloS one · 2014Article
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 functional significance of the widespread down-regulation of Rap1 GTPase-activating protein (Rap1GAP), a negative regulator of Rap activity, in human tumors is unknown. Here we show that human colon cancer cells depleted of Rap1GAP are endowed with more aggressive migratory and invasive properties. Silencing Rap1GAP enhanced the migration of confluent and single cells. In the latter, migration distance, velocity, and directionality were increased. Enhanced migration was a consequence of increased endogenous Rap activity as silencing Rap expression selectively abolished the migration of Rap1GAP-depleted cells. ROCK-mediated cell contractility was suppressed in Rap1GAP-depleted cells, which exhibited a spindle-shaped morphology and abundant membrane protrusions. Tumor cells can switch between Rho/ROCK-mediated contractility-based migration and Rac1-mediated mesenchymal motility. Strikingly, the migration of Rap1GAP-depleted, but not control cells required Rac1 activity, suggesting that loss of Rap1GAP alters migratory mechanisms. Inhibition of Rac1 activity restored membrane blebbing and increased ROCK activity in Rap1GAP-depleted cells, suggesting that Rac1 contributes to the suppression of contractility. Collectively, these findings identify Rap1GAP as a critical regulator of aggressive tumor cell behavior and suggest that the level of Rap1GAP expression influences the migratory mechanisms that are operative in tumor cells.
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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.