ArticleOncotarget2016
Regulation of the epithelial to mesenchymal transition and metastasis by Raf kinase inhibitory protein-dependent Notch1 activity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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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.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- The protease inhibitor gabexate mesylate targets Raf kinase inhibitor protein and reverses epithelial-mesenchymal transition in triple-negative breast cancer cells.Frontiers in oncology · 2026Article
- Review
- Clinical Significance of Frequently Down-Regulated Phosphatidylethanolamine-Binding Protein-1 in Gallbladder Cancer.Digestive diseases and sciences · 2024Article
- Manipulating RKIP reverses the metastatic potential of breast cancer cells.Frontiers in oncology · 2023Article
- Review
- Autophagy-mediated degradation of NOTCH1 intracellular domain controls the epithelial to mesenchymal transition and cancer metastasis.Cell & bioscience · 2022Article
- Review
- PEBP1/RKIP behavior: a mirror of actin-membrane organization.Cellular and molecular life sciences : CMLS · 2020Article
- Current Status of Raf Kinase Inhibitor Protein (RKIP) in Lung Cancer: Behind RTK Signaling.Cells · 2019Review
- Molecular alterations of cancer cell and tumour microenvironment in metastatic gastric cancer.Oncogene · 2018Review
- RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact.Cancers · 2018Review
- A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics.Critical reviews in oncogenesis · 2018Review
- miR-19b promotes breast cancer metastasis through targeting MYLIP and its related cell adhesion molecules.Oncotarget · 2017Article
- "Stealth dissemination" of macrophage-tumor cell fusions cultured from blood of patients with pancreatic ductal adenocarcinoma.PloS one · 2017Article
- Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling.Tzu chi medical journalReview
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Raf kinase inhibitory protein (RKIP), an endogenous inhibitor of the extracellular signal-regulated kinase (ERK) pathway, has been implicated as a suppressor of metastasis and a prognostic marker in cancers. However, how RKIP acts as a suppressor during metastasis is not fully understood. Here, we show that RKIP activity in cervical and stomach cancer is inversely correlated with endogenous levels of the Notch1 intracellular domain (NICD), which stimulates the epithelial to mesenchymal transition (EMT) and metastasis. The levels of RKIP were significantly decreased in tumor tissues compared to normal tissues, whereas NICD levels were increased. Overexpression of RKIP in several cell lines resulted in a dramatic decrease of NICD and subsequent inhibition of several mesenchymal markers, such as vimentin, N-cadherin, and Snail. In contrast, knockdown of RKIP exhibited opposite results both in vitro and in vivo using mouse models. Nevertheless, knockdown of Notch1 in cancer cells had no effect on the expression of RKIP, suggesting that RKIP is likely an upstream regulator of the Notch1 pathway. We also found that RKIP directly interacts with Notch1 but has no influence on the intracellular level of the γ-secretase complex that is necessary for Notch1 activation. These data suggest that RKIP plays a distinct role in activation of Notch1 during EMT and metastasis, providing a new target for cancer treatment.
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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.