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Syk Tyrosine Kinase Is Linked to Cell Motility and Progression in Squamous Cell Carcinomas of the Head and Neck

Sutima Luangdilok¹, Carol Box¹, Lisa Patterson¹, William Court¹, Kevin Harrington^2,3, Lisa Pitkin³, Peter Rhs-Evans³, Pornchai O-charoenrat⁴ and Suzanne Eccles¹

¹ Tumour Biology and Metastasis Team, Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, McElwain Laboratories, Sutton, Surrey, United Kingdom; ² Targeted Therapy Team, Section of Cell and Molecular Biology, Chester Beatty Laboratories; ³ Head and Neck Unit, Royal Marsden Hospital, London, United Kingdom; and ⁴ Division of Head and Neck Surgery, Department of Surgery, Siriraj Hospital Medical School, Bangkok, Thailand

Requests for reprints: Suzanne Eccles, McElwain Laboratories, The Institute of Cancer Research, 15 Cotswold Road, Belmont, Sutton, Surrey SM2 5NG, United Kingdom. Phone: 44-20-8722-4210; Fax: 44-20-8722-4134; E-mail: Sue.Eccles{at}icr.ac.uk.

Syk, a non–receptor tyrosine kinase, is an important component of immunoreceptor signaling in hematopoietic cells. It has been implicated in key regulatory pathways including phosphoinositide 3-kinase and phospholipase C (PLC) activation in B cells and integrin signaling in platelets and bronchial epithelial cells. Recently, potential roles in cancer have been reported. In breast cancers, reduced Syk expression was associated with invasion, and its overexpression in cell lines was shown to inhibit cell motility. In contrast, Syk has been shown to mediate chemomigration in nasopharyngeal carcinoma cells. Its role in squamous cell carcinomas of the head and neck (SCCHN) has not yet been investigated. Syk mRNA and protein expression was detected in 6 of 10 SCCHN cell lines. When Syk was transfected into Syk-negative cells (SIHN-011A), chemomigration was enhanced in vitro and this was associated with activation of PLC1. Conversely, abrogation of Syk activity by pharmacologic inhibition or small interfering RNA in HN6 cells with high levels of endogenous expression inhibited migration, haptotaxis, and engagement with matrix proteins; this was accompanied by decreased levels of phosphorylated AKT. Similar effects were seen in Syk-positive CAL 27 cells but not in Syk-negative SIHN-011A cells. Immunoprecipitation suggested co-association of Syk with epidermal growth factor receptor and GRB-2. Syk expression in SCCHN patient tissues was examined by semiquantitative real-time PCR (n = 45) and immunohistochemistry (n = 38) in two independent cohorts. Higher levels of Syk expression were observed in tumors and lymph node metastases relative to normal tissues. High Syk expression significantly correlated with worse survival and may be of prognostic value in SCCHN due to its potential role in cell migration and invasion. [Cancer Res 2007;67(16):7907–16]

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