Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran; Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Pathol Res Pract. 2024 Oct;262:155558. doi: 10.1016/j.prp.2024.155558. Epub 2024 Aug 26.
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.
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 通路的组成性激活可以促进不受控制的细胞增殖并阻止细胞凋亡，从而促进肿瘤的发展。JAK-STAT 通路的激活受到几种调节分子的控制，特别是由八个成员组成的细胞因子信号转导抑制物 (SOCS) 家族，包括 SOCS1-SOCS7 和细胞因子诱导的 SH2 结构域蛋白 (CIS)。在前列腺癌细胞中，SOCS1-SOCS3、SOCS5-SOCS7 以及 CIS 的异常表达同样也可以通过不同的方式引发各种细胞信号通路的启动，特别是 JAK-STAT3、MAPK、ERK，从而促进细胞增殖、迁移、侵袭和活力；细胞周期进展；上皮间质转化；血管生成；对治疗的抵抗；免疫逃逸；以及肿瘤微环境中的慢性炎症，这些都会导致肿瘤的进展、转移和预后不良。表观遗传修饰，主要是由于 DNA 甲基化、microRNAs、促炎细胞因子、生长因子和雄激素，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抵抗并提高现有治疗方法的疗效。在这篇综述中，我们全面解释了 SOCS 在前列腺癌中的失调，以深入了解 SOCS 蛋白失调的机制。这些知识可能为通过恢复和调节 SOCS 分子的表达来开发管理前列腺癌的新治疗策略铺平道路。
