CHI3L1

Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted is_associated_with::glycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1 is_associated_with::gene. The name YKL-40 is derived from the three N-terminal is_associated_with::amino acids present on the secreted form and its is_associated_with::molecular mass. YKL-40 is secreted by various cell-types including is_associated_with::macrophages, is_associated_with::chondrocytes, and some types of is_associated_with::cancer cells. YKL-40 lacks is_associated_with::chitinase activity due to mutations within the active site (conserved sequence: DXXDXDXE ; YKL-40 sequence: DGLDLAWL). The exact physiological role of YKL-40 is not known, but it has been implicated in development, inflammatory disease (such as is_associated_with::asthma, and cancer progression).

Function
is_associated_with::Chitinases catalyze the hydrolysis of is_associated_with::chitin, which is an abundant glycopolymer found in insect exoskeletons and fungal cell walls. The glycoside hydrolase 18 family of chitinases includes eight human family members. This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated is_associated_with::macrophages, is_associated_with::chondrocytes, is_associated_with::neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling.

Regulation and mechanism
YKL-40 has been linked to activation of the is_associated_with::AKT pro-survival (anti-apoptotic) signaling pathway.

YKL-40 is a migration factor for primary is_associated_with::astrocytes and its expression is controlled by NFI-X3, is_associated_with::STAT3, and AP-1.

Role in cancer
YKL-40 is a Th2 promoting is_associated_with::cytokine that is present at high levels in the is_associated_with::tumor micro-environment and in the serum of cancer patients. Elevated levels of YKL-40 correlate strongly with stage and outcome of various types of cancer, which establish YKL-40 as a biomarker of disease severity. Targeting YKL-40 with neutralizing antibodies has been proven effective as a treatment in animal models of is_associated_with::glioblastoma multiforme. YKL-40 is able to promote angiogenesis through VEGF-dependent and independent pathways.

YKL-40 also enhances tumor survival in response to gamma-irradiation.