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Leukemia inhibitory factor (LIF) is a polyfunctional glycoprotein and member of the IL-6 superfamily of cytokines. LIF binds to the LIF receptor (LIFR) and gp130 to exert its effects through multiple signal transduction pathways including JAK/STAT3, PI3K/AKT, ERK1/2, and mTOR. LIF receptors can be found in liver, bone, uterus, kidney, and nerve tissue. Its association with major signal transduction pathways and presence in multiple tissues explain LIF’s many pleiotropic effects, which include roles in development, self-renewal, metabolism, tumor progression, and inflammation. Although LIF has been shown to inhibit Leukemia, the effect of LIF has on cancer depends on the type. LIF can promote metastasis in certain cancers of the skin, breast, uterus, and bone. Cyokine-mediated expression of LIF leads to the breakdown of cartilage in articular chondrocytes. This inflammatory process may be responsible for the cartilage degradation observed in rheumatoid arthritis.