ArticleThe Journal of biological chemistry2012
Zyxin is a transforming growth factor-β (TGF-β)/Smad3 target gene that regulates lung cancer cell motility via integrin α5β1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 72 citations in OpenAlex.
- Zyxin protects against hypertensive nephropathy by restraining FAK/Skp2-CDK8/YAP signaling in tubular epithelial cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis.Nature communications · 2026Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Endothelial knockdown of the tumor suppressor,American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Zyxin is important for the stability and function of podocytes, especially during mechanical stretch.Communications biology · 2024Article
- The role of zyxin in signal transduction and its relationship with diseases.Frontiers in molecular biosciences · 2024Review
- TGF-β1 signalling in Alzheimer's pathology and cytoskeletal reorganization: a specialized Tau perspective.Journal of neuroinflammation · 2023Review
- Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition.International journal of molecular sciences · 2022Article
- Expression of Zyxin in Non-Small Cell Lung Cancer-A Preliminary Study.Biomolecules · 2022Article
- Canonical TGFβ signaling induces collective invasion in colorectal carcinogenesis through a Snail1- and Zeb1-independent partial EMT.Oncogene · 2022Article
- The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems.Cell communication and signaling : CCS · 2021Review
- Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins.International journal of molecular sciences · 2021Article
- Actin Cytoskeleton and Regulation of TGFβ Signaling: Exploring Their Links.Biomolecules · 2021Review
- Integrin alpha-2 and beta-1 expression increases through multiple generations of the EDW01 patient-derived xenograft model of breast cancer-insight into their role in epithelial mesenchymal transition in vivo gained from an in vitro model system.Breast cancer research : BCR · 2020Article
- Prognostic values of SNAI family members in breast cancer patients.Annals of translational medicine · 2020Article
- MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer.International journal of molecular sciences · 2020Review
- MAP2K1 is a potential therapeutic target in erlotinib resistant head and neck squamous cell carcinoma.Scientific reports · 2019Article
- Crosstalk between cancer and immune cells: Role of tumor-associated macrophages in the tumor microenvironment.Cancer medicine · 2019Review
- Phosphoproteomic Profiling Identifies Aberrant Activation of Integrin Signaling in Aggressive Non-Type Bladder Carcinoma.Journal of clinical medicine · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although TGF-β acts as a tumor suppressor in normal tissues and in early carcinogenesis, these tumor suppressor effects are lost in advanced malignancies. Single cell migration and epithelial-mesenchymal transition (EMT), both of which are regulated by TGF-β, are critical steps in mediating cancer progression. Here, we sought to identify novel direct targets of TGF-β signaling in lung cancer cells and have indentified the zyxin gene as a target of Smad3-mediated TGF-β1 signaling. Zyxin concentrates at focal adhesions and along the actin cytoskeleton; as such, we hypothesized that cytoskeletal organization, motility, and EMT in response to TGF-β1 might be regulated by zyxin expression. We show that TGF-β1 treatment of lung cancer cells caused rapid phospho-Smad3-dependent expression of zyxin. Zyxin expression was critical for the formation and integrity of cell adherens junctions. Silencing of zyxin decreased expression of the focal adhesion protein vasodilator-activated phospho-protein (VASP), although the formation and morphology of focal adhesions remained unchanged. Zyxin-depleted cells displayed significantly increased integrin α5β1 levels, accompanied by enhanced adhesion to fibronectin and acquisition of a mesenchymal phenotype in response to TGF-β1. Zyxin silencing led to elevated integrin α5β1-dependent single cell motility. Importantly, these features are mirrored in the K-ras-driven mouse model of lung cancer. Here, lung tumors revealed decreased levels of both zyxin and phospho-Smad3 when compared with normal tissues. Our data thus demonstrate that zyxin is a novel functional target and effector of TGF-β signaling in lung cancer. By regulating cell-cell junctions, integrin α5β1 expression, and cell-extracellular matrix adhesion, zyxin may regulate cancer cell motility and EMT during lung cancer development and progression.
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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.