ArticleScientific reports2016
hnRNPK inhibits GSK3β Ser9 phosphorylation, thereby stabilizing c-FLIP and contributes to TRAIL resistance in H1299 lung adenocarcinoma cells.
Article in Scientific reports, 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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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression to impede the progression of lung adenocarcinoma.Cell death & disease · 2025Article
- Exosomal PPARγ derived from macrophages suppresses LPS-induced peritonitis by negative regulation of CD14/TLR4 axis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Tumor suppressor mediated ubiquitylation of hnRNPK is a barrier to oncogenic translation.Nature communications · 2022Article
- TRIM21-regulated Annexin A2 plasma membrane trafficking facilitates osteosarcoma cell differentiation through the TFEB-mediated autophagy.Cell death & disease · 2021Article
- Heterogeneous nuclear ribonucleoprotein K is overexpressed and contributes to radioresistance irrespective of HPV status in head and neck squamous cell carcinoma.International journal of molecular medicine · 2020Article
- Cytoplasmic PCNA is located in the actin belt and involved in osteoclast differentiation.Aging · 2020Article
- Proximity proteomics identifies cancer cell membrane cis-molecular complex as a potential cancer target.Cancer science · 2019Article
- Review
- hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing.Cancer cell international · 2019Article
- Up-regulation of exosomal miR-125a in pneumoconiosis inhibits lung cancer development by suppressing expressions of EZH2 and hnRNPK.RSC advances · 2018Article
- hnRNP K plays a protective role in TNF-α-induced apoptosis in podocytes.Bioscience reports · 2018Article
- Glycogen synthase kinase-3β inhibition promotes lysosome-dependent degradation of c-FLIPCell death & disease · 2018Article
- cFLIP critically modulates apoptotic resistance in epithelial-to-mesenchymal transition.Oncotarget · 2017Article
- Heterogeneous nuclear ribonucleoprotein K is associated with poor prognosis and regulates proliferation and apoptosis in bladder cancer.Journal of cellular and molecular medicine · 2017Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
c-FLIP (cellular FLICE-inhibitory protein) is the pivotal regulator of TRAIL resistance in cancer cells, It is a short-lived protein degraded through the ubiquitin/proteasome pathway. The discovery of factors and mechanisms regulating its protein stability is important for the comprehension of TRAIL resistance by tumor cells. In this study, we show that, when H1299 lung adenocarcinoma cells are treated with TRAIL, hnRNPK is translocated from nucleus to cytoplasm where it interacts and co-localizes with GSK3β. We find that hnRNPK is able to inhibit the Ser9 phosphorylation of GSK3β by PKC. This has the effect of activating GSK3β and thereby stabilizing c-FLIP protein which contributes to the resistance to TRAIL in H1299 cells. Our immunohistochemical analysis using tissue microarray provides the clinical evidence of this finding by establishing a negative correlation between the level of hnRNPK expression and the Ser9 phosphorylation of GSK3β in both lung adenocarcinoma tissues and normal tissues. Moreover, in all cancer tissues examined, hnRNPK was found in the cytoplasm whereas it is exclusively nuclear in the normal tissues. Our study sheds new insights on the molecular mechanisms governing the resistance to TRAIL in tumor cells, and provides new clues for the combinatorial chemotherapeutic interventions with TRAIL.
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