Role of SOCS1 in tumor progression and therapeutic application

Abstract

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 cytokineinitiated 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.

SOCS proteins in regulation of receptor tyrosine kinase signaling

“…The expression of SOCS1 is absence in normal skin or melanocytic nevi while up-regulated in melanoma and related to tumor invasion as well as stage of the disease indicating that SOCS1 has prognostic significance in melanoma [79]. In contrast, the expression of SOCS1 was down-regulated in pancreatic cancer, acute myeloid leukemia, multiple myeloma, lymphoma and hepatocellular carcinoma [80,81]. In the latter case, this seems to be explained by aberrant methylation of SOCS1 promoter [23].…”

Clinical Relevance of SOCS1 and SOCS3 in Patients with Oral Squamous Cell Carcinoma

“…Also, in patients with colorectal cancer, papillary thyroid cancer, glioblastoma primary tissues, breast cancer and hepatocellular carcinoma tumors protein expression of SOCS1 and SOCS3 (Sasi et al, 2010;Wu et al, 2011;Ayyildiz et al, 2014;Kobawala et al, 2017). On the other hand, decreased SOCS1 and SOCS3 expression is observed in various cancers, including prostate cancer, hepatocellular carcinoma, laryngeal carcinoma, multiple myeloma, acute myeloid leukemia, pancreatic cancer and lymphoma (Mottok et al, 2009;Zhang et al, 2012). Although, these discrepancies existed in expression of SOCS proteins are still unknown.…”

SOCS1 gene mutations in patients with diffuse large B-cell lymphoma

“…Имеются противоречивые данные об изменении уровня экспрессии белка SOCS1 в опухолевых клетках. Уменьшение экс-прессии белка SOCS1 выявляется при раке различной локализа-ции, а также при гемобластозах (множественной миеломе, остром миелоидном лейкозе и лимфомах) [29,30]. Исследование, выполненное у больных раком простаты, выявило уменьшение экспрессии белка SOCS1 после андрогенной супрессии и повы-шение экспрессии его у пациентов при рецидивах [30].…”

“…Гиперметилирование про-моутера гена SOCS1 обнаруживается при различных онкологиче-ских заболеваниях, таких как гепатоцеллюлярная карцинома, рак поджелудочной железы, меланома, острый миелоидный лейкоз, множественная миелома, рак яичников, рак желудка и РМЖ же-лезы [30,[36][37][38][39]. Гиперметилирование самого гена SOCS1 выяв-лено при некоторых типах лимфом и миелодиспластическом синдроме [40,41].…”