Keewan Esra'a, Matlawska-Wasowska Ksenia
Department of Pediatrics, Division of Hematology and Oncology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Comprehensive Cancer Center, University of New Mexico, Albuquerque, NM 87131, USA.
Cancers (Basel). 2021 Aug 8;13(16):4000. doi: 10.3390/cancers13164000.
Cytokines are pleiotropic signaling molecules that execute an essential role in cell-to-cell communication through binding to cell surface receptors. Receptor binding activates intracellular signaling cascades in the target cell that bring about a wide range of cellular responses, including induction of cell proliferation, migration, differentiation, and apoptosis. The Janus kinase and transducers and activators of transcription (JAK/STAT) signaling pathways are activated upon cytokines and growth factors binding with their corresponding receptors. The SOCS family of proteins has emerged as a key regulator of cytokine signaling, and SOCS insufficiency leads to constitutive activation of JAK/STAT signaling and oncogenic transformation. Dysregulation of SOCS expression is linked to various solid tumors with invasive properties. However, the roles of SOCS in hematological malignancies, such as leukemia, are less clear. In this review, we discuss the recent advances pertaining to SOCS dysregulation in leukemia development and progression. We also highlight the roles of specific SOCS in immune cells within the tumor microenvironment and their possible involvement in anti-tumor immunity. Finally, we discuss the epigenetic, genetic, and post-transcriptional modifications of SOCS genes during tumorigenesis, with an emphasis on leukemia.
细胞因子是多效性信号分子，通过与细胞表面受体结合在细胞间通讯中发挥重要作用。受体结合激活靶细胞内的信号级联反应，引发广泛的细胞反应，包括诱导细胞增殖、迁移、分化和凋亡。细胞因子和生长因子与其相应受体结合后，可激活Janus激酶和转录激活因子（JAK/STAT）信号通路。SOCS蛋白家族已成为细胞因子信号传导的关键调节因子，SOCS功能不足会导致JAK/STAT信号通路的组成性激活和致癌转化。SOCS表达失调与具有侵袭性的各种实体瘤有关。然而，SOCS在血液系统恶性肿瘤（如白血病）中的作用尚不清楚。在本综述中，我们讨论了白血病发生和发展过程中SOCS失调的最新进展。我们还强调了特定SOCS在肿瘤微环境中免疫细胞中的作用及其可能参与抗肿瘤免疫的情况。最后，我们讨论了肿瘤发生过程中SOCS基因的表观遗传、遗传和转录后修饰，重点是白血病。
