Role of SOCS1 in tumor progression and therapeutic application.
SOCS1, a prototype molecule of the SOCS family, was initially defined as a suppressor of cytokine signaling. The molecular mechanisms of SOCS1-mediated functions have been subsequently identified by studies using gene knockout mice and gene silencing technology. As part of a negative feedback regulation, SOCS1 downregulates cytokine signaling through direct inhibition of the JAK tyrosine kinase and the signaling cascade of activated cytokine receptors, thereby attenuating cytokine-initiated signal transduction. Moreover, other studies have demonstrated that SOCS1 also downregulates TLR signaling through direct and indirect mechanisms. Both cytokine receptor and TLR signaling pathways mediate important functions in survival, maturation and differentiation of various types of cells and in the regulation of immune function. Abnormal expression of SOCS1 in tumor cells has been detected in various human cancers, where it is associated with dysregulation of cytokine receptor and TLR signaling to promote cell transformation. Recent studies on the function of SOCS1 in tumor cells have revealed its novel role in carcinogenesis. In this review, we will focus on the mechanism of action of SOCS1 in both tumor cells and antigen-presenting cells in the tumor microenvironment. The potential of using SOCS1 as a diagnostic marker and therapeutic target in tumor diagnosis, prognosis and treatment is discussed.
Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Jing
J
Zhang
Hui
H
Li
Jin-Pu
JP
Yu
Shizhen Emily
SE
Wang
Xiu-Bao
XB
Ren
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018121:Receptors, Cytokine; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors