ArticleNature cancer2023
Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS.
Article in Nature cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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66 citing papers in PubMed, 80 citations in OpenAlex.
- Multi-Modal Kinome Profiling Discovers Mesenchymal-Like Polarity Networks that Underly Directed Hepatocellular Carcinoma Cell Migration.bioRxiv : the preprint server for biology · 2026Article
- RAS-targeted therapies for pancreatic cancer.ESMO gastrointestinal oncology · 2026Review
- Phosphorylated HPV‑16 E7 disrupts planar cell polarity in cervical cancer cells through vangl1 dysregulation.PLoS pathogens · 2026Article
- Article
- Cross-species insights from ART-D to uncover evolutionarily conserved oncogenic mechanisms.Molecular systems biology · 2026Article
- Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in colorectal cancer.Cancer cell · 2026Article
- Cyclin K condensates bridge CDK12 to phosphorylate and drive oncogenic YAP activation in hepatocellular carcinoma.Science advances · 2026Article
- Overcoming Adaptive Resistance to KRASG12D Blockade in Pancreatic Cancer through Vertical Pathway Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRASScientific reports · 2026Article
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Cetuximab co-treatment with KRAS G12C inhibitors fulzerasib and sotorasib in human KRAS G12C non-small cell lung cancer cells.Cell death discovery · 2026Article
- Exploring biomarkers of mitochondrial dynamics in polycystic ovary syndrome and the effect of mesenchymal stem cell transplantation on ovarian mitochondria.Journal of ovarian research · 2026Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- KRAS-Driven Hypertranscription and Metastatic Dissemination in Colorectal Cancer Could be Overcome by Targeting the NMHC IIA/ PLK1 Signaling Axis with a Novel Acridine Derivative.International journal of biological sciences · 2026Article
- Targeting KRAS Inhibitor-Resistant Pancreatic Cancer with an MUC1-C Antibody-Drug Conjugate.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Intrinsic resistance to RAS inhibitors is driven by dysregulation of KRAS degradation.Nature communications · 2025Article
- AND logic-gated CRISPR/Cas9 and hybridization chain reaction system for precise ctDNA detection.Journal of nanobiotechnology · 2025Article
- IFN-γ-driven UBE2D3 upregulation impairs antigen presentation pathways and anti-tumor immunity in pancreatic cancer.Nature communications · 2025Article
- Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor cells evade targeted drugs by rewiring their genetic and epigenetic networks. Here, we identified that inhibition of MAPK signaling rapidly induces an epithelial-to-mesenchymal transition program by promoting re-localization of an apical-basal polarity protein, Scribble, in oncogene-addicted lung cancer models. Mis-localization of Scribble suppressed Hippo-YAP signaling, leading to YAP nuclear translocation. Furthermore, we discovered that a RAS superfamily protein MRAS is a direct target of YAP. Treatment with KRAS G12C inhibitors induced MRAS expression, which formed a complex with SHOC2, precipitating feedback activation of MAPK signaling. Abrogation of YAP activation or MRAS induction enhanced the efficacy of KRAS G12C inhibitor treatment in vivo. These results highlight a role for protein localization in the induction of a non-genetic mechanism of resistance to targeted therapies in lung cancer. Furthermore, we demonstrate that induced MRAS expression is a key mechanism of adaptive resistance following KRAS G12C inhibitor treatment.
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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.