ArticleNature communications2013
PKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis.
Article in Nature communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.PLoS computational biology · 2025Article
- Muscone Reduces OGD/R-Induced Hyperpermeability of the Brain Endothelial Barrier by Activating the PKA/RHOA/MLC Pathway.Current neurovascular research · 2025Article
- The focal adhesion protein talin is a mechanically gated A-kinase anchoring protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FBXO28 suppresses liver cancer invasion and metastasis by promoting PKA-dependent SNAI2 degradation.Oncogene · 2023Article
- SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP.Nature communications · 2022Article
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Comprehensive understanding of anchorage-independent survival and its implication in cancer metastasis.Cell death & disease · 2021Review
- Structural basis for p50RhoGAP BCH domain-mediated regulation of Rho inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RLIP76: A Structural and Functional Triumvirate.Cancers · 2021Review
- DLC1 SAM domain-binding peptides inhibit cancer cell growth and migration by inactivating RhoA.The Journal of biological chemistry · 2020Article
- PTBP1-mediated regulation of AXL mRNA stability plays a role in lung tumorigenesis.Scientific reports · 2019Article
- Receptor tyrosine kinase activation of RhoA is mediated by AKT phosphorylation of DLC1.The Journal of cell biology · 2017Article
- Resveratrol inhibits proliferation and migration through SIRT1 mediated post‑translational modification of PI3K/AKT signaling in hepatocellular carcinoma cells.Molecular medicine reports · 2017Article
- Resveratrol inhibits age-dependent spontaneous tumorigenesis by SIRT1-mediated post-translational modulations in the annual fishOncotarget · 2017Article
- Regulating Rho GTPases and their regulators.Nature reviews. Molecular cell biology · 2016Review
- AMPK and PKA interaction in the regulation of survival of liver cancer cells subjected to glucose starvation.Oncotarget · 2016Article
- Epidermal growth factor activates the Rho GTPase-activating protein (GAP) Deleted in Liver Cancer 1 via focal adhesion kinase and protein phosphatase 2A.The Journal of biological chemistry · 2015Article
- Deleted in liver cancer-1 (DLC1): an emerging metastasis suppressor gene.Molecular diagnosis & therapy · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deleted in Liver Cancer 1 (DLC1) is a tumour suppressor that encodes a RhoGTPase-activating protein (RhoGAP) and is frequently inactivated in many human cancers. The RhoGAP activity of DLC1 against Rho signalling is well documented and is strongly associated with the tumour suppressor functions of DLC1. However, the mechanism by which the RhoGAP activity of DLC1 is regulated remains obscure. Here, we report that phosphorylation of DLC1 at Ser549 by cyclic AMP-dependent protein kinase A contributes to enhanced RhoGAP activity and promotes the activation of DLC1, which suppresses hepatoma cell growth, motility and metastasis in both in vitro and in vivo models. Intriguingly, we found that Ser549 phosphorylation induces the dimerization of DLC1 and that inducible dimerization of DLC1 can rescue the tumour suppressive and RhoGAP activities of DLC1 containing a Ser549 deletion. Our study establishes a novel regulatory mechanism for DLC1 RhoGAP activity via dimerization induced by protein kinase A signalling.
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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.