ArticleScientific reports2016
The microRNA-200/Zeb1 axis regulates ECM-dependent β1-integrin/FAK signaling, cancer cell invasion and metastasis through CRKL.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 74 citations in OpenAlex.
- Role of ZEB1 in angiogenesis and therapeutic potential (Review).International journal of molecular medicine · 2026Review
- The miR-8/miR-200 family: from functional diversification to translational applications.Cellular & molecular biology letters · 2026Review
- ZEB1, a novel junctional adhesion molecule A regulator, impacts sensitivity of pancreatic cancer-associated fibroblasts to reovirus.Molecular therapy. Oncology · 2025Article
- The Redox-Adhesion-Exosome (RAX) Hub in Cancer: Lipid Peroxidation-Driven EMT Plasticity and Ferroptosis Defense with HNE/MDA Signaling and Lipidomic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- Identification of an extracellular matrix signature for predicting prognosis and sensitivity to therapy of patients with gastric cancer.Scientific reports · 2025Article
- siRNA-based strategies to combat drug resistance in gastric cancer.Medical oncology (Northwood, London, England) · 2024Review
- The Nexus of Inflammation-Induced Epithelial-Mesenchymal Transition and Lung Cancer Progression: A Roadmap to Pentacyclic Triterpenoid-Based Therapies.International journal of molecular sciences · 2023Review
- ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis.Molecular cancer research : MCR · 2023Article
- Targeting immunosuppressive Ly6C+ classical monocytes reverses anti-PD-1/CTLA-4 immunotherapy resistance.Frontiers in immunology · 2023Article
- Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis.Cell reports · 2022Article
- Osthole inhibits the migration and invasion of highly metastatic breast cancer cells by suppressing ITGα3/ITGβ5 signaling.Acta pharmacologica Sinica · 2022Article
- Review
- Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis.Cancers · 2022Review
- FAK in Cancer: From Mechanisms to Therapeutic Strategies.International journal of molecular sciences · 2022Review
- Transcriptional control of a collagen deposition and adhesion process that promotes lung adenocarcinoma growth and metastasis.JCI insight · 2022Article
- The significance of the crosstalk between ubiquitination or deubiquitination and ncRNAs in non-small cell lung cancer.Frontiers in oncology · 2022Review
- Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS-mutant lung cancer.JCI insight · 2021Article
- Dual Inhibition of MEK and AXL Targets Tumor Cell Heterogeneity and Prevents Resistant Outgrowth Mediated by the Epithelial-to-Mesenchymal Transition in NSCLC.Cancer research · 2021Article
- MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy.Biomolecules · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Tumor cell metastasis is a complex process that has been mechanistically linked to the epithelial-mesenchymal transition (EMT). The double-negative feedback loop between the microRNA-200 family and the Zeb1 transcriptional repressor is a master EMT regulator, but there is incomplete understanding of how miR-200 suppresses invasion. Our recent efforts have focused on the tumor cell-matrix interactions essential to tumor cell activation. Herein we utilized both our Kras/p53 mutant mouse model and human lung cancer cell lines to demonstrate that upon miR-200 loss integrin β1-collagen I interactions drive 3D in vitro migration/invasion and in vivo metastases. Zeb1-dependent EMT enhances tumor cell responsiveness to the ECM composition and activates FAK/Src pathway signaling by de-repression of the direct miR-200 target, CRKL. We demonstrate that CRKL serves as an adaptor molecule to facilitate focal adhesion formation, mediates outside-in signaling through Itgβ1 to drive cell invasion, and inside-out signaling that maintains tumor cell-matrix contacts required for cell invasion. Importantly, CRKL levels in pan-cancer TCGA analyses were predictive of survival and CRKL knockdown suppressed experimental metastases in vivo without affecting primary tumor growth. Our findings highlight the critical ECM-tumor cell interactions regulated by miR-200/Zeb1-dependent EMT that activate intracellular signaling pathways responsible for tumor cell invasion and metastasis.
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.