Suppressors of cytokine signalling 1–7 (SOCS1–7) and cytokine-inducible SH2-containing protein (CIS) are a group of intracellular proteins that are well known as JAK-STAT and several other signalling pathways negative feedback regulators. More recently several members have been identified as tumour suppressors and dysregulation of their biological roles in controlling cytokine and growth factor signalling may contribute to the development of many solid organ and haematological malignancies. This review explores their biological functions and their possible tumour suppressing role in human neoplasms. 1. Cytokines and Their Signalling Pathways Cytokines are a large family of secreted soluble glycoproteins that regulate cellular growth and differentiation which are part of fundamental biological processes including embryonic development, immunity, wound healing, and haematopoiesis. Cytokines carry information about the biological status to target cells by interacting with receptors on the cell surface. Cellular responses to cytokine stimulation depend on the type of cytokine and the nature of the target cell and include proliferation, differentiation, effector function, and survival [1, 2]. Cytokines activate multiple intracellular signalling pathways in order to produce their physiological effects. One of the most studied pathways is that involving the receptor-associated janus kinases (JAKs) and the latent cytoplasmic transcription factors signal transducers and activators of transcription (STATs) [3, 4]. Genetic deletion experiments in mice have demonstrated that this pathway is critical for the actions of specific cytokines. For example, STAT1 is absolutely required for the actions of interferons, STAT4 is absolutely necessary for the actions of interleukin-12 (IL-12), STAT6 is required for the actions of interleukin-4 (IL-4), and JAK3 is required for the actions of cytokines that use the common γ receptor [5]. This cascade requires strict cellular control and loss of regulation can promote tumorigenesis and chronic inflammation. The threshold, magnitude, and specific responses elicited by cytokine stimulation are regulated by numerous mechanisms including tyrosine phosphatases, receptor internalisation, proteasomal degradation of signalling adaptor molecules, soluble receptor antagonists, and specific inhibitors, including the protein inhibitors of activated STATs (PIAS) and suppressor of cytokine signalling (SOCS) proteins. The expression of SOCS proteins can be induced by cytokine stimulation, and they not only serve to interfere with signalling
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