ArticleOncotarget2014
Identification of a ternary protein-complex as a therapeutic target for K-Ras-dependent colon cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 26 citations in OpenAlex.
- G-quadruplex structural dynamics at MAPK12 promoter dictates transcriptional switch to determine stemness in breast cancer.Cellular and molecular life sciences : CMLS · 2024Article
- Review
- Sensitivity of Oncogenic KRAS-Expressing Cells to CDK9 Inhibition.SLAS discovery : advancing life sciences R & D · 2021Article
- Article
- Post-translational modifications of Hsp90 and translating the chaperone code.The Journal of biological chemistry · 2020Review
- Dynamically Shaping Chaperones. Allosteric Modulators of HSP90 Family as Regulatory Tools of Cell Metabolism in Neoplastic Progression.Frontiers in oncology · 2020Review
- Neratinib augments the lethality of [regorafenib + sildenafil].Journal of cellular physiology · 2019Article
- Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.Acta pharmaceutica Sinica. B · 2018Review
- The K-Ras effector p38γ MAPK confers intrinsic resistance to tyrosine kinase inhibitors by stimulatingThe Journal of biological chemistry · 2017Article
- Multi-kinase inhibitors can associate with heat shock proteins through their NH2-termini by which they suppress chaperone function.Oncotarget · 2016Article
- Article
- Role of cancer-associated fibroblasts in invasion and metastasis of gastric cancer.World journal of gastroenterology · 2015Review
- p38γ MAPK Is a Therapeutic Target for Triple-Negative Breast Cancer by Stimulation of Cancer Stem-Like Cell Expansion.Stem cells (Dayton, Ohio) · 2015Article
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
A cancer phenotype is driven by several proteins and targeting a cluster of functionally interdependent molecules should be more effective for therapeutic intervention. This is specifically important for Ras-dependent cancer, as mutated (MT) Ras is non-druggable and targeting its interaction with effectors may be essential for therapeutic intervention. Here, we report that a protein-complex activated by the Ras effector p38γ MAPK is a novel therapeutic target for K-Ras-dependent colon cancer. Unbiased proteomic screening and immune-precipitation analyses identified p38γ interaction with heat shock protein 90 (Hsp90) and K-Ras in K-Ras MT, but not wild-type (WT), colon cancer cells, indicating a role of this complex in Ras-dependent growth. Further experiments showed that this complex requires p38γ and Hsp90 activity to maintain MT, but not WT, K-Ras protein expression. Additional studies demonstrated that this complex is activated by p38γ-induced Hsp90 phosphorylation at S595, which is important for MT K-Ras stability and for K-Ras dependent growth. Of most important, pharmacologically inhibition of Hsp90 or p38γ activity disrupts the complex, decreases K-Ras expression, and selectively inhibits the growth of K-Ras MT colon cancer in vitro and in vivo. These results demonstrated that the p38γ-activated ternary complex is a novel therapeutic target for K-Ras-dependent colon cancer.
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Registered trials
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