SYK is a nonreceptor tyrosine kinase containing two adjacent Src homology 2 (SH2) domains, a kinase domain, but no SH3 domain. SYK is expressed in hematopoietic cells where it binds phosphorylated immunoreceptor tyrosine-based activation motifs (ITAM) to mediate immune receptor signaling. For malignant hematopoietic cells that rely on immune receptormediated survival signals, SYK might represent an attractive drug target. Indeed, pharmacologic inhibition of SYK has shown promising results in the context of non-Hodgkin lymphoma and leukemias. SYK is also widely expressed in a variety of cell types outside the hematopoietic system and it is required for proper development of blood and lymph vessels during embryonic development. The role of SYK in epithelial cancers appears diverse. SYK abundance negatively correlates with breast cancer progression and SYK suppresses tumor growth and metastasis in breast cancer xenografts. Conversely, SYK levels in head and neck squamous cell carcinomas and lymph node metastases are high compared with corresponding normal tissue and SYK promotes migration of squamous carcinoma cells.
Koerber R M, Held S A E, Heine A, et al. Analysis of the anti-proliferative and the pro-apoptotic efficacy of Syk inhibition in multiple myeloma[J]. Experimental hematology & oncology, 2015, 4(1): 1.