ArticleArchives of otolaryngology--head & neck surgery2010
Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling.
Article in Archives of otolaryngology--head & neck surgery, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- Article
- Review
- Tumour cells express functional lymphatic endothelium-specific hyaluronan receptor in vitro and in vivo: Lymphatic mimicry promotes oral oncogenesis?Oncogenesis · 2021Article
- The role of alternative splicing in human cancer progression.American journal of cancer research · 2021Review
- Head and neck cancer management and cancer stem cells implication.The Saudi dental journal · 2019Review
- 4-Methylumbelliferone Inhibits Cancer Stem Cell Activation and Overcomes Chemoresistance in Ovarian Cancer.Cancers · 2019Article
- Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer.Experimental & molecular medicine · 2019Review
- Differing Roles of Hyaluronan Molecular Weight on Cancer Cell Behavior and Chemotherapy Resistance.Cancers · 2018Review
- Microgravity-Induced Alterations of Inflammation-Related Mechanotransduction in Endothelial Cells on Board SJ-10 Satellite.Frontiers in physiology · 2018Article
- ΔNp63-mediated regulation of hyaluronic acid metabolism and signaling supports HNSCC tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Akt Signaling Is Sustained by a CD44 Splice Isoform-Mediated Positive Feedback Loop.Cancer research · 2017Article
- Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways.International journal of medical sciences · 2017Article
- Intratracheal Administration of Hyaluronan-Cisplatin Conjugate Nanoparticles Significantly Attenuates Lung Cancer Growth in Mice.Pharmaceutical research · 2016Article
- xCT expression modulates cisplatin resistance in Tca8113 tongue carcinoma cells.Oncology letters · 2016Article
- The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer.Stem cells international · 2016Review
- The Extracellular Matrix in Epithelial Ovarian Cancer - A Piece of a Puzzle.Frontiers in oncology · 2015Review
- The Role of CD44 in Disease Pathophysiology and Targeted Treatment.Frontiers in immunology · 2015Review
- Expression of CD147 and Lewis y antigen in ovarian cancer and their relationship to drug resistance.Medical oncology (Northwood, London, England) · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectivesTo investigate whether hyaluronan (HA), a ligand for the transmembrane receptor CD44, and CD44, which acts through multiple signaling pathways to influence cellular behavior, promote Rho kinase- and phosphatidylinositol 3 (PI-3) kinase-mediated oncogenic signaling to alter cisplatin sensitivity and stimulate tumor cell proliferation, migration, and matrix metalloproteinase secretion in head and neck squamous cell carcinoma (HNSCC).
designLaboratory investigation using the HNSCC cell line HSC-3.
settingUniversity laboratory.
main outcome measuresRho kinase and PI-3 kinase activity, myosin phosphatase and AKT phosphorylation, tumor cell growth, migration, and matrix metalloproteinase secretion were measured in the presence or absence of HA, cisplatin, and inhibitors of Rho kinase and PI-3 kinase.
resultsThe addition of HA, but not HA plus anti-CD44 antibody, resulted in increased Rho kinase and PI-3 kinase activity. Results of immunoblotting studies demonstrated that HA promotes Rho kinase-mediated myosin phosphatase phosphorylation and PI-3 kinase-mediated AKT phosphorylation. Hyaluronan was shown to promote migration and increased matrix metalloproteinase secretion through Rho kinase-mediated signaling. Hyaluronan treatment promoted increased tumor proliferation and resulted in a 12-fold reduced ability of cisplatin to cause HNSCC cell death. On the other hand, the presence of Y-27632, a Rho kinase inhibitor, and LY-294002, a PI-3 kinase inhibitor, blocked HA-mediated cisplatin resistance by HNSCC.
conclusionsOur results suggest that HA and CD44 promote Rho kinase- and PI-3 kinase-mediated oncogenic signaling and cisplatin resistance. Perturbation of HA-CD44-mediated Rho kinase and PI-3 kinase signaling pathways may be a novel strategy to treat HNSCC.
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Registered trials
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