ArticleOncotarget2017
A novel ZEB1/HAS2 positive feedback loop promotes EMT in breast cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.Biomolecules · 2026Review
- Extracellular matrix mediates circulating tumor cell clustering in triple-negative breast cancer metastasis.Nature communications · 2026Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- The role of ESRP1 in solid tumor development through the regulation of CD44 splicing and EMT processes.Frontiers in oncology · 2025Review
- Emerging roles of circular RNAs in the invasion and metastasis of head and neck cancer: Possible functions and mechanisms.Cancer innovation · 2023Review
- Oligometastases: Characterizing the Role of Epigenetic Regulation of Epithelial-Mesenchymal Transition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.Nature communications · 2023Article
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Weaving the nest: extracellular matrix roles in pre-metastatic niche formation.Frontiers in oncology · 2023Review
- The role of the ZEB1-neuroinflammation axis in CNS disorders.Journal of neuroinflammation · 2022Review
- High Levels of Hyaluronic Acid Synthase-2 Mediate NRF2-Driven Chemoresistance in Breast Cancer Cells.Biomolecules & therapeutics · 2022Article
- Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis.Cancers · 2022Review
- miR-223-3p targets FBXW7 to promote epithelial-mesenchymal transition and metastasis in breast cancer.Thoracic cancer · 2022Article
- The effect of COVID-19 derived cytokine storm on cancer cells progression: double-edged sword.Molecular biology reports · 2022Review
- Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis.Biomolecules · 2021Review
- Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis.Cancer gene therapy · 2021Article
- Deregulation of Transcription Factor Networks Driving Cell Plasticity and Metastasis in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
- Increased SPHK1 and HAS2 Expressions Correlate to Poor Prognosis in Pancreatic Cancer.BioMed research international · 2021Article
- Decorin deficiency promotes epithelial-mesenchymal transition and colon cancer metastasis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Hybrid E/M Phenotype(s) and Stemness: A Mechanistic Connection Embedded in Network Topology.Journal of clinical medicine · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer metastasis is the main reason for poor patient survival. Tumor cells delaminate from the primary tumor by induction of epithelial-mesenchymal transition (EMT). EMT is mediated by key transcription factors, including ZEB1, activated by tumor cell interactions with stromal cells and the extracellular matrix (ECM). ZEB1-mediated EMT and motility is accompanied by substantial cell reprogramming and the acquisition of a stemness phenotype. However, understanding of the underlying mechanism is still incomplete. We identified hyaluronic acid (HA), one major ECM proteoglycan and enriched in mammary tumors, to support EMT and enhance ZEB1 expression in cooperation with CD44s. In breast cancer cell lines HA is synthesized mainly by HAS2, which was already shown to be implicated in cancer progression. ZEB1 and HAS2 expression strongly correlates in various cancer entities and high HAS2 levels associate with an early relapse. We identified HAS2, tumor cell-derived HA and ZEB1 to form a positive feedback loop as ZEB1, elevated by HA, directly activates HAS2 expression. In an in vitro differentiation model HA-conditioned medium of breast cancer cells is enhancing osteoclast formation, an indicator of tumor cell-induced osteolysis that facilitates formation of bone metastasis. In combination with the previously identified ZEB1/ESRP1/CD44s feedback loop, we found a novel autocrine mechanism how ZEB1 is accelerating EMT.
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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.