RHAMM/ERK interaction induces proliferative activities of cementifying fibroma cells through a mechanism based on the CD44–EGFR

Autor: Nobuyuki Kamata, Koichiro Higashikawa, Hideo Shigeishi, Kei Tobiume, Yasusei Kudo, Hiroko Hatano, Takashi Takata
Rok vydání: 2011
Předmět:
MAPK/ERK pathway
Cell
Cell Cycle Proteins
Protein Serine-Threonine Kinases
Biology
Ligands
Epiregulin
Pathology and Forensic Medicine
Aurora Kinases
medicine
Humans
Gene Silencing
RNA
Messenger
Hyaluronic Acid
Phosphorylation
RNA
Small Interfering
Extracellular Signal-Regulated MAP Kinases
Molecular Biology
Cell Line
Transformed
Cell Proliferation
Oligonucleotide Array Sequence Analysis
Cell Nucleus
Extracellular Matrix Proteins
Epidermal Growth Factor
Cell growth
Cell adhesion molecule
Gene Expression Profiling
CD44
Nuclear Proteins
Cell Biology
medicine.disease
Hyaluronan-mediated motility receptor
Enzyme Activation
ErbB Receptors
body regions
stomatognathic diseases
Hyaluronan Receptors
medicine.anatomical_structure
Mitogen-activated protein kinase
Fibroma
Ossifying
biology.protein
Cancer research
Fibroma
Microtubule-Associated Proteins
Protein Processing
Post-Translational
Signal Transduction
Zdroj: Laboratory Investigation. 91:379-391
ISSN: 0023-6837
DOI: 10.1038/labinvest.2010.176
Popis: We have previously established immortalized cells (HCF) from cementifying fibroma of the jaw bone. Here, we found that the receptor for hyaluronan (HA)-mediated motility (RHAMM) and epiregulin, a ligand for the epidermal growth factor receptor (EGFR), were highly expressed in HCF cells in comparison with osteoblasts by conducting a microarray analysis. The cell growth of HCF cells was significantly decreased by the knockdown of RHAMM using small interfering RNA (siRNA). RHAMM was associated with extracellular signal-regulated kinase (ERK) and essential for ERK phosphorylation. HCF cells had characteristic growth mechanisms in which epiregulin functions in an extracellular autocrine loop. Interestingly, exogenous HA induced the phosphorylation of EGFR, which was mainly dependent on CD44. The results raise the novel idea that the EGFR may activate Raf-MEK-ERK signaling in response to the binding of HA to CD44. Moreover, RHAMM was able to associate with TPX2 in the nucleus and was required for HA-induced activation of the Aurora A kinase. The results suggest that RHAMM has a predominant role in the cell cycle in HCF. Here, we report the new machinery by which RHAMM/ERK interaction induces the proliferative activity of cementifying fibroma cells via a specific signaling pathway through the CD44-EGFR axis.
Databáze: OpenAIRE
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