ArticleOncotarget2015
K-Ras stabilization by estrogen via PKCδ is involved in endometrial tumorigenesis.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- AIMP2-DX2 provides therapeutic interface to control KRAS-driven tumorigenesis.Nature communications · 2022Article
- Small Molecule Destabilizer of β-Catenin and Ras Proteins Antagonizes Growth of K-Ras Mutation-Driven Colorectal Cancers Resistant to EGFR Inhibitors.Targeted oncology · 2020Article
- Small molecule-induced simultaneous destabilization of β-catenin and RAS is an effective molecular strategy to suppress stemness of colorectal cancer cells.Cell communication and signaling : CCS · 2020Article
- Construction and Characterization of KRAS Immune Lipid Magnetic Balls for Colorectal Cancer Circulating Tumor Cells.Cancer management and research · 2020Article
- WDR76 mediates obesity and hepatic steatosis via HRas destabilization.Scientific reports · 2019Article
- Article
- WDR76 is a RAS binding protein that functions as a tumor suppressor via RAS degradation.Nature communications · 2019Article
- BKCa participates in E2 inducing endometrial adenocarcinoma by activating MEK/ERK pathway.BMC cancer · 2018Article
- Rottlerin inhibits cell growth and invasion via down-regulation of EZH2 in prostate cancer.Cell cycle (Georgetown, Tex.) · 2018Article
- Stabilization of Sur8 via PKCα/δ degradation promotes transformation and migration of colorectal cancer cells.Oncotarget · 2017Article
- Co-dependency of PKCδ and K-Ras: inverse association with cytotoxic drug sensitivity in KRAS mutant lung cancer.Oncogene · 2017Article
- Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia.Theranostics · 2017Article
- KY1022, a small molecule destabilizing Ras via targeting the Wnt/β-catenin pathway, inhibits development of metastatic colorectal cancer.Oncotarget · 2016Article
- Rottlerin exerts its anti-tumor activity through inhibition of Skp2 in breast cancer cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogens are considered as a major risk factor of endometrial cancer. In this study, we identified a mechanism of tumorigenesis in which K-Ras protein is stabilized via estrogen signaling through the ER-α36 receptor. PKCδ was shown to stabilize K-Ras specifically via estrogen signaling. Estrogens stabilize K-Ras via inhibition of polyubiquitylation-dependent proteasomal degradation. Estrogen-induced cellular transformation was abolished by either K-Ras or PKCδ knockdown. The role of PKCδ in estrogen-induced tumorigenesis was confirmed in a mouse xenograft model by reduction of tumors after treatment with rottlerin, a PKCδ inhibitor. Finally, levels of PKCδ correlated with that of Ras in human endometrial tumor tissues. Stabilization of K-Ras by estrogen signaling involving PKCδ up-regulation provides a potential therapeutic approach for treatment of endometrial cancer.
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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.