ArticleOncogene2014
The Ron receptor tyrosine kinase activates c-Abl to promote cell proliferation through tyrosine phosphorylation of PCNA in breast cancer.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Elucidation of the Role of SHMT2 in L-Serine Homeostasis in Hypoxic Hepa1-6 Cells.International journal of molecular sciences · 2024Article
- GRB2 stabilizes RAD51 at reversed replication forks suppressing genomic instability and innate immunity against cancer.Nature communications · 2024Article
- Loss of tyrosine 211 phosphorylation of proliferating cell nuclear antigen (PCNA) enhances postnatal mammary gland development.BioMedicine · 2024Article
- A network map of macrophage-stimulating protein (MSP) signaling.Journal of cell communication and signaling · 2023Article
- Plasma membrane proteoglycans syndecan-2 and syndecan-4 engage with EGFR and RON kinase to sustain carcinoma cell cycle progression.The Journal of biological chemistry · 2022Article
- The Functions of PCNA in Tumor Stemness and Invasion.International journal of molecular sciences · 2022Article
- RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.World journal of gastroenterology · 2021Review
- Post-Translational Modifications of PCNA in Control of DNA Synthesis and DNA Damage Tolerance-the Implications in Carcinogenesis.International journal of biological sciences · 2021Review
- RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion.Frontiers in oncology · 2021Article
- RON and MET Co-overexpression Are Significant Pathological Characteristics of Poor Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Triple-Negative Breast Cancer.Cancer research and treatment · 2020Article
- Targeting RON receptor tyrosine kinase for treatment of advanced solid cancers: antibody-drug conjugates as lead drug candidates for clinical trials.Therapeutic advances in medical oncology · 2020Review
- Phosphoproteome profiling revealed abnormally phosphorylated AMPK and ATF2 involved in glucose metabolism and tumorigenesis of GH-PAs.Journal of endocrinological investigation · 2019Article
- MiR-216a-5p targets TCTN1 to inhibit cell proliferation and induce apoptosis in esophageal squamous cell carcinoma.Cellular & molecular biology letters · 2019Article
- EnABLing Tumor Growth and Progression: Recent progress in unraveling the functions of ABL kinases in solid tumor cells.Current pharmacology reports · 2018Article
- Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage.The Journal of biological chemistry · 2017Article
- Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork.Molecular cell · 2017Review
- Role of β-Interferon Inducer (DEAE-Dextran) in Tumorigenesis by VEGF and NOTCH1 Inhibition along with Apoptosis Induction.Frontiers in pharmacology · 2017Article
- Prognostic value and clinicopathological significance of proliferating cell nuclear antigen expression in gastric cancer: a systematic review and meta-analysis.OncoTargets and therapy · 2017Article
- Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.Journal of cancer research and clinical oncology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple growth pathways lead to enhanced proliferation in malignant cells. However, how the core machinery of DNA replication is regulated by growth signaling remains largely unclear. The sliding clamp proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA machinery responsible for replicating the genome and maintaining genomic integrity. We previously reported that epidermal growth factor receptor (EGFR) triggered tyrosine 211 (Y211) phosphorylation of PCNA, which in turn stabilized PCNA on chromatin to promote cell proliferation. Here we show that the phosphorylation can also be catalyzed by the non-receptor tyrosine kinase c-Abl. We further demonstrate that, in the absence of EGFR, signaling to PCNA can be attained through the activation of the Ron receptor tyrosine kinase and the downstream non-receptor tyrosine kinase c-Abl. We show that Ron and c-Abl form a complex, and that activation of Ron by its ligand, hepatocyte growth factor-like protein (HGFL), stimulates c-Abl kinase activity, which in turn directly phosphorylates PCNA at Y211 and leads to an increased level of chromatin-associated PCNA. Correspondingly, HGFL-induced Ron activation resulted in Y211 phosphorylation of PCNA while silencing of c-Abl blocked this effect. We show that c-Abl and Y211 phosphorylation of PCNA is an important axis downstream of Ron, which is required for cell proliferation. Treatment with a specific peptide that inhibits Y211 phosphorylation of PCNA or with the c-Abl pharmacological inhibitor imatinib suppressed HGFL-induced cell proliferation. Our findings identify the pathway of Ron-c-Abl-PCNA as a mechanism of oncogene-induced cell proliferation, with potentially important implications for development of combination therapy of breast cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.