ArticleCell death and differentiation2019
MEK nuclear localization promotes YAP stability via sequestering β-TrCP in KRAS mutant cancer cells.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Basroparib inhibits YAP-driven cancers by stabilizing angiomotin.Molecular oncology · 2026Article
- Novel function of GTPBP2 in promoting hepatocellular carcinoma progression through inhibition of BTRC-mediated KRAS degradation.Cancer cell international · 2026Article
- ARHGEF3 coordinates adipocyte hypertrophy and differentiation through dual YAP-RhoA and PPARγ activation.Journal of advanced research · 2026Article
- Epithelioid Hemangioendothelioma: Treatment Landscape and Innovations for an Ultra-Rare Sarcoma.Current treatment options in oncology · 2025Review
- Mutational Landmarks in Anaplastic Thyroid Cancer: A Perspective of a New Treatment Strategy.Journal of clinical medicine · 2025Review
- Review
- Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.Acta pharmaceutica Sinica. B · 2024Article
- Ampelopsis grossedentata tea alleviating liver fibrosis in BDL-induced mice via gut microbiota and metabolite modulation.NPJ science of food · 2024Article
- Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases.Cancers · 2024Article
- Overcoming BRAF and CDK4/6 inhibitor resistance by inhibiting MAP3K3-dependent protection against YAP lysosomal degradation.Experimental & molecular medicine · 2024Article
- Therapeutic strategies to overcomeFrontiers in oncology · 2024Article
- Ubiquitinomics revealed disease- and stage-specific patterns relevant for the 3PM approach in human sigmoid colon cancers.The EPMA journal · 2023Article
- Review
- Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer.Molecular cancer · 2021Review
- Review
- Ursodeoxycholic acid suppresses the malignant progression of colorectal cancer through TGR5-YAP axis.Cell death discovery · 2021Article
- MINDY1 promotes bladder cancer progression by stabilizing YAP.Cancer cell international · 2021Article
- Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment.Journal of experimental & clinical cancer research : CR · 2021Article
- YAP Circular RNA, circYap, Attenuates Cardiac Fibrosis via Binding with Tropomyosin-4 and Gamma-Actin Decreasing Actin Polymerization.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Landscape and dynamics of single tumor and immune cells in early and advanced-stage lung adenocarcinoma.Clinical and translational medicine · 2021Article
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
Tumours manage to survive the ablation of mutant KRAS, despite the development of KRAS-targeted drugs. Here we describe that inhibition of mutant KRAS promotes MEK nuclear localization as an alternative mechanism of KRAS-targeted drugs resistance. Tissue microarray analysis in colon tumours shows that aberrant MEK nuclear localization is closely related to YAP levels and tumour malignancy. MEK nuclear localization could sequester β-TrCP from cytoplasmic inactive YAP, then stabilizing YAP. Mutant KRAS restrains MEK within the cytoplasm via IQGAP1, inhibiting MEK nuclear translocation. Trametinib, an allosteric MEK inhibitor, could prevent MEK nuclear localization and subsequently promote YAP degradation. In vitro and in vivo results suggests that inhibition of MEK nuclear localization by trametinib synergizes with KRAS knockdown or deltarasin treatment in suppressing the viability of KRAS mutant colon cancer cells. Our study provides new insights into the mechanisms of resistance to KRAS ablation, and suggests novel strategies for the treatment of KRAS-mutant colon cancers.
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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.