ArticleCancer research2010
Estrogen suppresses MLK3-mediated apoptosis sensitivity in ER+ breast cancer cells.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 32 citations in OpenAlex.
- Selective Degradation of MLK3 by a Novel CEP1347-VHL-02 PROTAC Compound Limits the Oncogenic Potential of TNBC.Journal of medicinal chemistry · 2024Article
- MLK3 localizes mainly to the cytoplasm and promotes oxidative stress injury via a positive feedback loop.Cell biochemistry and biophysics · 2023Article
- TrkA expression directs the anti-neoplastic activity of MLK3 inhibitors in triple-negative breast cancer.Oncogene · 2023Article
- Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.Oncogene · 2021Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- MLK3 Is Associated With Poor Prognosis in Patients With Glioblastomas and Actin Cytoskeleton Remodeling in Glioblastoma Cells.Frontiers in oncology · 2020Article
- Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates.Molecules (Basel, Switzerland) · 2018Review
- Transcriptional regulation of mixed lineage kinase 3 by estrogen and its implication in ER-positive breast cancer pathogenesis.Oncotarget · 2017Article
- Human Epidermal Growth Factor Receptor 2 (HER2) Impedes MLK3 Kinase Activity to Support Breast Cancer Cell Survival.The Journal of biological chemistry · 2015Article
- Mixed lineage kinase 3 deficient mice are protected against the high fat high carbohydrate diet-induced steatohepatitis.Liver international : official journal of the International Association for the Study of the Liver · 2014Article
- Targeting Cdc42 in cancer.Expert opinion on therapeutic targets · 2013Review
- Mixed Lineage Kinase-c-Jun N-Terminal Kinase Axis: A Potential Therapeutic Target in Cancer.Genes & cancer · 2013Review
- Increased JNK in males compared with females in a rodent model of abdominal aortic aneurysm.The Journal of surgical research · 2012Article
- Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- MLK4 has negative effect on TLR4 signaling.Cellular & molecular immunology · 2012Article
- Cdc42 and Rac1 are major contributors to the saturated fatty acid-stimulated JNK pathway in hepatocytes.Journal of hepatology · 2012Article
- Mixed lineage kinase 3 modulates β-catenin signaling in cancer cells.The Journal of biological chemistry · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Little knowledge exists about the mechanisms by which estrogen can impede chemotherapy-induced cell death of breast cancer cells. 17beta-Estradiol (E(2)) hinders cytotoxic drug-induced cell death in estrogen receptor-positive (ER(+)) breast cancer cells. We noted that the activity of the proapoptotic mixed lineage kinase 3 (MLK3) kinase was relatively higher in estrogen receptor-negative (ER(-)) breast tumors, suggesting that E(2) might inhibit MLK3 activity. The kinase activities of MLK3 and its downstream target, c-Jun NH(2)-terminal kinase, were rapidly inhibited by E(2) in ER(+) but not in ER(-) cells. Specific knockdown of AKT1/2 prevented MLK3 inhibition by E(2), indicating that AKT mediated this event. Furthermore, MLK3 inhibition by E(2) involved phosphorylation of MLK3 Ser(674) by AKT, attenuating the proapoptotic function of MLK3. We found that a pan-MLK inhibitor (CEP-11004) limited Taxol-induced cell death and that E(2) accentuated this limitation. Taken together, our findings indicate that E(2) inhibits the proapoptotic function of MLK3 as a mechanism to limit cytotoxic drug-induced death of ER(+) breast cancer cells.
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.