肿瘤微环境中存在不同类型的细胞因子、生长因子或激素，它们可以通过与其特定的细胞表面受体结合来激活 JAK-STAT 信号通路。 JAK-STAT 通路的组成型激活可以促进不受控制的细胞增殖并防止细胞凋亡，从而导致肿瘤发展。 JAK-STAT 通路的激活由多种调节分子控制，特别是由八个成员组成的细胞因子信号传导抑制因子 (SOCS) 家族，其中包括 SOCS1-SOCS7 和含有细胞因子诱导型 SH2 (CIS) 蛋白。在前列腺癌细胞中，SOCS1-SOCS3、SOCS5-SOCS7以及CIS的不规则表达可以相似且不同地导致各种细胞信号通路（特别是JAK-STAT3、MAPK、ERK）的启动，从而促进细胞增殖，迁移、入侵和生存能力；细胞周期进展；上皮-间质转化；血管生成；对治疗有抵抗力；免疫逃避；肿瘤微环境内的慢性炎症导致肿瘤进展、转移和预后不良。主要由DNA甲基化、微小RNA、促炎细胞因子、生长因子和雄激素引起的表观遗传修饰可以影响前列腺癌细胞中SOCS分子的表达。使用调节、恢复或增强 SOCS 蛋白表达的策略可能有助于克服治疗耐药性并提高现有疗法的疗效。在这篇综述中，我们对前列腺癌中 SOCS 失调进行了全面的解释，以深入了解 SOCS 蛋白失调的机制。这些知识可能为开发新的治疗策略铺平道路，通过恢复和调节 SOCS 分子的表达来控制前列腺癌。版权所有 © 2024 Elsevier GmbH。版权所有。

Different types of cytokines, growth factors, or hormones present within the tumor microenvironment that can activate the JAK-STAT signaling pathway by binding to their specific cell surface receptors. The constitutive activation of the JAK-STAT pathway can promote uncontrolled cell proliferation and prevent apoptosis contributing to tumor development. Activation of the JAK-STAT pathway is controlled by several regulatory molecules, particularly the suppressor of cytokine signaling (SOCS) family consisting of eight members, which include SOCS1-SOCS7 and the cytokine-inducible SH2-containing (CIS) proteins. In prostate cancer cells, the irregular expression of the SOCS1-SOCS3, SOCS5-SOCS7 as well as CIS can similarly and differentially result in the initiation of various cellular signaling pathways (in particular JAK-STAT3, MAPK, ERK) that promote cell proliferation, migration, invasion and viability; cell cycle progression; epithelial-mesenchymal transition; angiogenesis; resistance to therapy; immune evasion; and chronic inflammation within the tumor microenvironment which lead to tumor progression, metastasis and poor prognosis. Epigenetic modifications, mainly due to DNA methylation, microRNAs, pro-inflammatory cytokines, growth factors and androgens can influence the expression of the SOCS molecules in prostate cancer cells. Using strategies to modulate, restore or enhance the expression of SOCS proteins, may help overcome treatment resistance and improve the efficacy of existing therapies. In this review, we provide a comprehensive explanation regarding SOCS dysregulation in prostate cancer to provide insights into the mechanisms underlying the dysregulation of SOCS proteins. This knowledge may pave the way for the development of novel therapeutic strategies to manage prostate cancer by restoring and modulating the expression of SOCS molecules.Copyright © 2024 Elsevier GmbH. All rights reserved.