ArticleOncotarget2014
SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Okanin Suppresses the Growth of Colorectal Cancer Cells by Targeting at Peroxiredoxin 5.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitin Ligases Siah1a/2 Control Alveolar Macrophage Functions to Limit Carcinogen-Induced Lung Adenocarcinoma.Cancer research · 2023Article
- The expression and the tumor suppressor role of CLDN6 in colon cancer.Molecular and cellular biochemistry · 2022Article
- SIAH2 regulates DNA end resection and replication fork recovery by promoting CtIP ubiquitination.Nucleic acids research · 2022Article
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- Expression of PD-L1 Is Associated with Inflammatory Microenvironment in Surgical Specimens of Non-Small Cell Lung Cancer.Journal of personalized medicine · 2021Article
- Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination.Viruses · 2021Review
- The emerging roles of E3 ubiquitin ligases in ovarian cancer chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Article
- TYK2: An Upstream Kinase of STATs in Cancer.Cancers · 2019Review
- Inhibition of Siah2 Ubiquitin Ligase by Vitamin K3 Attenuates Chronic Myeloid Leukemia Chemo-Resistance in Hypoxic Microenvironment.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Overriding TKI resistance of renal cell carcinoma by combination therapy with IL-6 receptor blockade.Oncotarget · 2017Article
- Article
- Global functional profiling of human ubiquitome identifies E3 ubiquitin ligase DCST1 as a novel negative regulator of Type-I interferon signaling.Scientific reports · 2016Article
- Molecular targets of luteolin in cancer.European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) · 2016Review
- The Steroidogenic Enzyme AKR1C3 Regulates Stability of the Ubiquitin Ligase Siah2 in Prostate Cancer Cells.The Journal of biological chemistry · 2015Article
- The Expression of the Ubiquitin Ligase SIAH2 (Seven In Absentia Homolog 2) Is Increased in Human Lung Cancer.PloS one · 2015Article
- STAT3 inhibition suppresses proliferation of retinoblastoma through down-regulation of positive feedback loop of STAT3/miR-17-92 clusters.Oncotarget · 2014Article
- A pan-cancer modular regulatory network analysis to identify common and cancer-specific network components.Cancer informatics · 2014Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets.
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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.