Size-dependent regulation of Snail2 by hyaluronan: Its role in cellular invasion

• Published in: Glycobiology (Oxford) Vol. 19; no. 8; pp. 890 - 898
• Main Authors: Craig, Evisabel A, Parker, Patti, Camenisch, Todd D
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2009; Oxford Publishing Limited (England)
• Subjects: Animals; CD44; Cell Movement - physiology; cellular invasion; Fibroblasts - metabolism; hyaluronan; Hyaluronan Receptors - metabolism; Hyaluronic Acid - metabolism; Mice; NF-kappa B - metabolism; NFκB; NIH 3T3 Cells; Original; Signal Transduction - physiology; Snail Family Transcription Factors; Snail2; Transcription Factors - metabolism; NFκB; cellular invasion; hyaluronan; CD44; Snail2
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/cwp064

Hyaluronan (HA) induces changes in cellular behavior that are crucial during both embryonic development and cancer progression. However, the biological effects of varying sizes of HA and the signal transduction mechanisms that these polymers may activate remain unclear. In this study, we demonstrate that pulse stimulation of mouse embryonic fibroblasts with high-molecular-weight (HMW) HA, but not HA of lower molecular sizes, leads to increases in Snail2 protein which are dependent on NFκB activity. Involvement of CD44, the main HA receptor, in these responses was determined by use of a CD44 blocking antibody and CD44 siRNA. Both the blockade and silencing of CD44 significantly abrogate the increases in nuclear factor kappaB (NFκB) activity and Snail2 protein following HMW-HA stimulation. Furthermore, we show that HMW-HA induces cellular invasion and that inhibition of CD44, Snail2, or NFκB significantly decreases this response. These studies elucidate a novel HA/Snail2 functional connection through CD44 and NFκB that is important for the induction of cellular invasion and is dependent on HA size.