ArticleMolecular carcinogenesis2019
Hyaluronan-CD44/RHAMM interaction-dependent cell proliferation and survival in lung cancer cells.
Article in Molecular carcinogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- Bridging Scales: Integrating Hyaluronan-Based Nanoencapsulation into 3D Hydrogel Constructs for Advanced Therapeutics-A Comprehensive Review.Gels (Basel, Switzerland) · 2026Review
- Hyaluronidase attenuates radiation-induced skin fibrosis through extracellular matrix remodeling and suppression of inflammatory-profibrotic signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.Biomolecules · 2026Review
- From steatosis to metastasis: microenvironmental reprogramming of the liver in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- Sustainable Production of High-Performance Antimicrobial Scaffold via an EngineeredBiomolecules · 2026Article
- Synergistic protective and regenerative effects of hyaluronic acid and polynucleotides against UVA-induced oxidative stress in dermal fibroblasts.Scientific reports · 2026Article
- TargetingbioRxiv : the preprint server for biology · 2025Article
- HMMR in human cancers: regulatory mechanism and biological function.Journal of translational medicine · 2025Review
- HMMR has oncoprotein-like properties in neuroblastoma cells and high HMMR expression has independent prognostic potential in neuroblastomas.Scientific reports · 2025Article
- Nicotine-Induced VEGF Levels in NSCLC Cells Are Modulated by PKA, Hyaluronan, and p53.International journal of molecular sciences · 2025Article
- Hepatocyte Growth Factor-Mediated Chondrocyte Proliferation Induced by Adipose-Derived MSCs from Osteoarthritis Patients and Its Synergistic Enhancement by Hyaluronic Acid.International journal of molecular sciences · 2025Article
- Hyaluronan accumulation is associated with reduced hyaluronidase expression in renal cell carcinoma, with CD44, HAS1, and HYAL2 emerging as prognostic markers.The journal of pathology. Clinical research · 2025Article
- Hyaluronan network remodeling by ZEB1 and ITIH2 enhances the motility and invasiveness of cancer cells.The Journal of clinical investigation · 2025Article
- The axis of tumor-associated macrophages, extracellular matrix proteins, and cancer-associated fibroblasts in oncogenesis.Cancer cell international · 2024Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Review
- The role of sialidase Neu1 in respiratory diseases.Respiratory research · 2024Review
- Identification of crosstalk genes relating to ECM-receptor interaction genes in MASH and DN using bioinformatics and machine learning.Journal of cellular and molecular medicine · 2024Article
- Multiple aspects of matrix stiffness in cancer progression.Frontiers in oncology · 2024Review
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Although members of the hyaluronan (HA)-CD44/HA-mediated motility receptor (RHAMM) signaling pathway have been shown to be overexpressed in lung cancer, their role in lung tumorigenesis is unclear. In the present study, we first determined levels of HA and its receptors CD44 and RHAMM in human non-small cell lung cancer (NSCLC) cells and stromal cells as well as mouse lung tumors. Subsequently, we examined the role of HA-CD44/RHAMM signaling pathway in mediating the proliferation and survival of NSCLC cells and the cross-talk between NSCLC cells and normal human lung fibroblasts (NHLFs)/lung cancer-associated fibroblasts (LCAFs). The highest levels of HA and CD44 were observed in NHLFs/LCAFs followed by NSCLC cells, whereas THP-1 monocytes/macrophages showed negligible levels of both HA and CD44. Simultaneous silencing of HA synthase 2 (HAS2) and HAS3 or CD44 and RHAMM suppressed cell proliferation and survival as well as the EGFR/AKT/ERK signaling pathway. Exogenous HA partially rescued the defect in cell proliferation and survival. Moreover, conditioned media (CM) generated by NHLFs/LCAFs enhanced the proliferation of NSCLC cells in a HA-dependent manner as treatment of NHLFs and LCAFs with HAS2 siRNA, 4-methylumbelliferone, an inhibitor of HASs, LY2228820, an inhibitor of p38MAPK, or treatment of A549 cells with CD44 blocking antibody suppressed the effects of the CM. Upon incubation in CM generated by A549 cells or THP-1 macrophages, NHLFs/LCAFs secreted higher concentrations of HA. Overall, our findings indicate that targeting the HA-CD44/RHAMM signaling pathway could be a promising approach for the prevention and therapy of lung cancer.
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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.