ArticleProceedings of the National Academy of Sciences of the United States of America2018
Zyxin promotes colon cancer tumorigenesis in a mitotic phosphorylation-dependent manner and through CDK8-mediated YAP activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Review
- Focal Adhesion and Cancer Cell Cycle-Associated Resistance.ACS omega · 2026Review
- Co-Immunoprecipitation-Coupled Mass Spectrometry Analysis of Zyxin's Interactome and Phosphosites in EarlyInternational journal of molecular sciences · 2026Article
- Targeting CDK8 dually enhances paclitaxel antitumor efficacy and alleviates chemotherapy-induced peripheral neuropathy in breast cancer.Frontiers in pharmacology · 2026Article
- In silico analysis of MALAT1 and H19 lncRNA interactions with the diabetes-related proteins ASK1 and YAP1.In silico pharmacology · 2026Article
- MED12 mutation induces RTK inhibitor resistance in NSCLC via MEK/ERK pathway activation by inflammatory cytokines.Cellular and molecular life sciences : CMLS · 2025Article
- Integrative High-Throughput RNAi Screening Identifies BRSK1, STK32C and STK40 as Novel Activators of YAP/TAZ.International journal of molecular sciences · 2025Article
- Posttranslational modifications of YAP/TAZ: molecular mechanisms and therapeutic opportunities.Cellular & molecular biology letters · 2025Review
- Synphilin-1 regulates mechanotransduction in rigidity sensing through interaction with zyxin.Journal of nanobiotechnology · 2025Article
- Synergistic Anticancer Strategy Targeting ECM Stiffness: Integration of Matrix Softening and Mechanical Signal Transduction Blockade in Primary Liver Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.The EMBO journal · 2024Article
- Decreased expression of p53 is associated with down expression of zyxin in breast cancer.Health science reports · 2024Article
- Unveiling the impact of CDK8 on tumor progression: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2024Review
- ASPP2 Is Phosphorylated by CDK1 during Mitosis and Required for Pancreatic Cancer Cell Proliferation.Cancers · 2023Article
- Zyxin inhibits the epithelial-mesenchymal transition process in gastric cancer by upregulating SIRT1.MedComm · 2023Article
- Zyxin Inhibits the Proliferation, Migration, and Invasion of Osteosarcoma via Rap1-Mediated Inhibition of the MEK/ERK Signaling Pathway.Biomedicines · 2023Article
- Non-hippo kinases: indispensable roles in YAP/TAZ signaling and implications in cancer therapy.Molecular biology reports · 2023Review
- Article
- Mena regulates nesprin-2 to control actin-nuclear lamina associations, trans-nuclear membrane signalling and gene expression.Nature communications · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Zyxin is a member of the focal adhesion complex and plays a critical role in actin filament polymerization and cell motility. Several recent studies showed that Zyxin is a positive regulator of Yki/YAP (Yes-associated protein) signaling. However, little is known about the mechanisms by which Zyxin itself is regulated and how Zyxin affects Hippo-YAP activity. We first showed that Zyxin is phosphorylated by CDK1 during mitosis. Depletion of Zyxin resulted in significantly impaired colon cancer cell proliferation, migration, anchorage-independent growth, and tumor formation in xenograft animal models. Mitotic phosphorylation is required for Zyxin activity in promoting growth. Zyxin regulates YAP activity through the colon cancer oncogene CDK8. CDK8 knockout phenocopied Zyxin knockdown in colon cancer cells, while ectopic expression of CDK8 substantially restored the tumorigenic defects of Zyxin-depletion cells. Mechanistically, we showed that CDK8 directly phosphorylated YAP and promoted its activation. Fully activated YAP is required to support the growth in CDK8-knockout colon cancer cells in vitro and in vivo. Together, these observations suggest that Zyxin promotes colon cancer tumorigenesis in a mitotic-phosphorylation-dependent manner and through CDK8-mediated YAP activation.
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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.