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.

Glioblastoma-derived Macrophage Colony-stimulating Factor (MCSF) Induces Microglial Release of Insulin-like Growth Factor-binding Protein 1 (IGFBP1) to Promote Angiogenesis

“…SYK plays a major role in survival signaling through multiple classes of immune recognition receptors in hematopoietic cells (46). However, SYK has been shown to act as both tumor promoter and tumor suppressor in different cancers (47). Whereas SYK activation generally involves recruitment through its Src homology 2 domains to a phosphorylated immune receptor tyrosine-based activation motif, it can also be activated by other mechanisms, such as elevated levels and its association with integrins (47).…”

MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88

“…18,19 Sykcoupled CLRs signaling induces PI3K/Akt, MAPK, NF-kB and inflammasome activation. 37,40,41 After engagement of TLRs, MyD88-dependent downstream signaling pathways activate MAPK and NF-kB. 17,19 Our Syk and MyD88 inhibition experiments in MV140-activated human DCs pointed out CLRs as the main drivers of Th17 and IL-10 immune responses in cooperation with TLRs.…”

Syk Is Recruited to Stress Granules and Promotes Their Clearance through Autophagy

“…The consequences of the presence or absence of Syk in tumor cells are manifested in different ways, depending on the tumor cell type and its stage of development (4). In many tumors, the expression of Syk enhances cell survival, especially in the face of external or internal factors, including oxidative stress, exposure to chemotherapeutic agents, expression of oncogenes like activated K-Ras, or loss of Rb (4,5,8,9).…”

“…In many tumors, the expression of Syk enhances cell survival, especially in the face of external or internal factors, including oxidative stress, exposure to chemotherapeutic agents, expression of oncogenes like activated K-Ras, or loss of Rb (4,5,8,9). Multiple mechanisms have been described to account for many of the protective effects of Syk on cells, including activation of the PI3K/Akt pro-survival pathway leading to the stabilization of the anti-apoptotic proteins Mcl-1 and/or XIAP, activation of mTOR, activation of STAT3 or STAT5, enhanced transcription of NF-B-regulated genes, and stabilization of the mRNA for Bcl-xL through an association of Syk with nucleolin (8, 9, 50 -56).…”