Calling in SYK: SYK's dual role as a tumor promoter and tumor suppressor in cancer

Abstract

SYK (spleen tyrosine kinase) is well-characterized in the immune system as an essential enzyme required for signaling through multiple classes of immune recognition receptors. As a modulator of tumorigenesis, SYK has a bit of a schizophrenic reputation, acting in some cells as a tumor promoter and in others as a tumor suppressor. In many hematopoietic malignancies, SYK provides an important survival function and its inhibition or silencing frequently leads to apoptosis. In cancers of non-immune cells, SYK provides a pro-survival signal, but can also suppress tumorigenesis by restricting epithelial-mesenchymal transition, enhancing cell-cell interactions and inhibiting migration.

Keywords: Apoptosis; Epithelial–mesenchymal transition; Protein phosphorylation; SYK; Signal transduction; Spleen tyrosine kinase.

Fig. 1

Mechanisms of SYK-promoted cell survival. SYK promotes the coupling of ITAM-bearing receptors to pro-survival pathways via the modulation of protein kinase activity ( ) leading to changes in the level of key regulators of apoptosis ( ) including increases in the production of anti-apoptotic proteins such as BCL-XL, MCL-1, BCL2A1, and XIAP; and a decrease in the pro-apoptotic protein HRK. SYK can also promote the activation of transcription factors ( ) such as STAT3, STAT5 and SREBP and enhance MYC-induced expression of microRNAs targeting ITIM-containing proteins such as CD22 and FCGR2B.