@article {29994,
	title = {Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion},
	journal = {J Biol ChemJ Biol Chem},
	volume = {286},
	number = {44},
	year = {2011},
	note = {Kouvidi, KaterinaBerdiaki, AikateriniNikitovic, DraganaKatonis, PavlosAfratis, NikosHascall, Vincent CKaramanos, Nikos KTzanakakis, George Neng2011/09/15J Biol Chem. 2011 Nov 4;286(44):38509-38520. doi: 10.1074/jbc.M111.275875. Epub 2011 Sep 13.},
	month = {Nov 4},
	pages = {38509-38520},
	edition = {20110913},
	abstract = {Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and receptor for hyaluronic acid-mediated motility (RHAMM) receptors. HA was recently found to regulate the migration of fibrosarcoma cells in a manner specifically dependent on its size. Here, we investigated the effect of HA/RHAMM signaling on the ability of HT1080 fibrosarcoma cells to adhere onto fibronectin. Low molecular weight HA (LMWHA) significantly increased (p </= 0.01) the adhesion capacity of HT1080 cells, which high molecular weight HA inhibited. The ability of HT1080 RHAMM-deficient cells, but not of CD44-deficient ones, to adhere was significantly decreased (p </= 0.001) as compared with control cells. Importantly, the effect of LMWHA on HT1080 cell adhesion was completely attenuated in RHAMM-deficient cells. In contrast, adhesion of RHAMM-deficient cells was not sensitive to high molecular weight HA treatment, which identifies RHAMM as a specific conduit of the LMWHA effect. Western blot and real time-PCR analyses indicated that LMWHA significantly increased RHAMM transcript (p </= 0.05) and protein isoform levels (53\%, 95 kDa; 37\%, 73 kDa) in fibrosarcoma cells. Moreover, Western blot analyses showed that LMWHA in a RHAMM-dependent manner enhanced basal and adhesion-dependent ERK1/2 and focal adhesion kinase (FAK) phosphorylation in HT1080 cells. Utilization of a specific ERK1/2 inhibitor completely inhibited (p </= 0.001) LMWHA-dependent adhesion, suggesting that ERK1/2 is a downstream effector of LMWHA/RHAMM signaling. Likewise, the utilization of the specific ERK1 inhibitor resulted in a strong down-regulation of FAK activation in HT1080 cells, which identifies ERK1/2 as a FAK upstream activator. In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways.},
	keywords = {*Gene Expression Regulation, Neoplastic, Cell Adhesion, Cell Line, Tumor, Extracellular Matrix Proteins/*chemistry, Fibrosarcoma/metabolism, Focal Adhesion Protein-Tyrosine Kinases/metabolism, Humans, Hyaluronan Receptors/*chemistry, Hyaluronic Acid/*chemistry, Mitogen-Activated Protein Kinase 1/metabolism, Mitogen-Activated Protein Kinase 3/metabolism, Molecular Weight, Oligosaccharides/chemistry, RNA, Small Interfering/metabolism, signal transduction},
	isbn = {1083-351X (Electronic)0021-9258 (Linking)},
	author = {Kouvidi, K. and Berdiaki, A. and Nikitovic, D. and Katonis, P. and Afratis, N. and Hascall, V. C. and Karamanos, N. K. and Tzanakakis, G. N.}
}
