Review
Immunology
Sunghark Kwon
Summary: JAKs are important enzymes in the JAK-STAT signaling pathway, and dysfunctional JAKs can lead to severe immune system-related diseases. Various JAK inhibitors have been developed to block abnormal JAK-STAT signaling, but drug selectivity and resistance to these inhibitors remain challenges. This review discusses the role and structure of JAKs, as well as strategies for disrupting JAK dimerization to develop novel inhibitors.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Xiaoxue Ma, Shingo Nakayamada
Summary: T follicular helper (Tfh) cells participate in humoral immune responses by promoting inflammation and aiding B cells survival, proliferation, maturation, and generation of autoantibodies. The plasticity of Tfh cells allows for adjustment of differentiation direction based on immune response level, regulated by various signaling factors such as cytokines, receptors, transcription factors, and genes. The STAT family signaling pathways play a crucial role in Tfh formation, with each member contributing to Tfh differentiation through mutual restraint and cooperation among cytokine-STAT signals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Chunguang Li, Maoling Zhu, Ji Zhu, Qijue Lu, Bowen Shi, Bin Sun, Hezhong Chen
Summary: SOX12 overexpression in ESCC is associated with malignant development, maintaining cell viability and enhancing mobility through activation of the JAK2/STAT3 signaling pathway. SOX12 may serve as a novel biomarker and candidate for targeted treatment in ESCC.
Review
Dermatology
Stephanie Chapman, Michael Kwa, Linda Stein Gold, Henry W. Lim
Summary: The JAK-STAT pathway is important in inflammatory dermatoses, and JAK inhibitors have shown efficacy in treating various dermatologic conditions.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ji-Rong Xie, Xiao-Jie Chen, Gang Zhou
Summary: Nuciferine shows potential as a therapeutic agent for oral squamous cell carcinoma (OSCC) by inhibiting cell growth and infiltration, and suppressing the STAT3 signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sarah M. M. AL-Qabbaa, Samaher I. I. Qaboli, Tahani K. K. Alshammari, Maha A. A. Alamin, Haya M. M. Alrajeh, Lama A. A. Almuthnabi, Rana R. R. Alotaibi, Asma S. S. Alonazi, Anfal F. F. Bin Dayel, Nawal M. M. Alrasheed, Nouf M. M. Alrasheed
Summary: This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on diabetic nephropathy (DN). The results showed that sitagliptin can reduce inflammation and improve DN by inhibiting PTP1B and modulating the JAK/STAT signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Mingyu Li, Shufang Jin, Zhiyuan Zhang, Hailong Ma, Xi Yang
Summary: IL-6 plays a critical role in regulating xCT gene in the carcinogenesis of head and neck squamous cell carcinoma, and its upregulation is associated with ferroptosis resistance. High expression of xCT is correlated with poor prognosis.
Review
Dermatology
Stephanie Chapman, Linda Stein Gold, Henry W. Lim
Summary: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is important in the development of inflammatory skin conditions, and JAK inhibitors have shown efficacy in treating various dermatologic diseases. This review focuses on JAK inhibitors being investigated for the treatment of alopecia areata, vitiligo, sarcoidosis, necrobiosis lipoidica, granuloma annulare, and systemic lupus erythematosus, with a discussion on safety and the implications of JAK inhibitors during the COVID-19 pandemic.
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Respiratory System
Qianqian Ju, Qinyan Shi, Cheng Liu, Guolong Fu, Hui Shi
Summary: This study investigated the effect and molecular mechanism of Bufalin on the proliferation, migration, and invasion of esophageal squamous cell carcinoma (ESCC) cells. The results showed that Bufalin inhibits ESCC cell progression through the PIAS3/STAT3 signaling pathway.
JOURNAL OF THORACIC DISEASE
(2023)
Article
Cell Biology
Zhendong Liu, Zhehao Fan, Rui Wang, Xiaolei Li, Hui Chen, Jingcheng Wang
Summary: This study investigated the effect of IFN-alpha-2b on preventing postoperative arthrofibrosis in rats and its antiproliferation effect on fibroblasts in vitro, as well as its molecular mechanism. The results showed that IFN-alpha-2b significantly reduced arthrofibrosis by inhibiting fibroblast proliferation and migration, possibly through the regulation of STAT1/p21 signaling pathway.
MEDIATORS OF INFLAMMATION
(2023)
Article
Oncology
Shuichi Tsukamoto, Yu-ichiro Koma, Yu Kitamura, Kohei Tanigawa, Yuki Azumi, Shoji Miyako, Satoshi Urakami, Masayoshi Hosono, Takayuki Kodama, Mari Nishio, Manabu Shigeoka, Hiroshi Yokozaki
Summary: Tumor-associated macrophages (TAMs) play a role in the progression of esophageal squamous cell carcinoma (ESCC). A direct co-culture system was used to study the interaction between ESCC cells and TAMs, revealing that matrix metalloproteinase 9 (MMP9) expression in ESCC cells was induced by direct co-culture with TAMs. MMP9 was associated with ESCC cell migration and invasion, and its expression was controlled by the Stat3 signaling pathway. Immunohistochemical analyses showed that MMP9 expression in cancer cells at the invasive front was related to high infiltration of M2-like TAMs and worse survival of patients. However, MMP9 expression in cancer stroma was not associated with any clinicopathological factors or patient prognoses.
Article
Pharmacology & Pharmacy
Ge Jin, Lintao Wang, Jun Ma
Summary: Cardiac hypertrophy is a compensatory response to chronic pressure overload, and excessive angiotensin II plays a significant role in inducing cardiac hypertrophy. Previous studies have shown that STAT5, a member of the STATs family, is closely linked to non-tumor diseases, but its specific role in hypertrophy progression remains unclear. In this study, STAT5-IN-1, a STAT5 inhibitor, was administered to mice and H9c2s cells were used as cell models to investigate the effects of STAT5-IN-1 on cardiac hypertrophy induced by angiotensin II. The findings demonstrated that STAT5 inhibitor substantially decreased cardiac hypertrophy by reducing inflammation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Cell Biology
Lena Puigdevall, Camille Michiels, Clara Stewardson, Laure Dumoutier
Summary: A subset of cytokines triggers the JAK-STAT pathway to exert various functions such as inflammation and immune responses. There are alternative modes of STAT activation, including association between the tyrosine-free region of cytokine receptors and STATs, and direct interaction between JAK and STAT proteins. These noncanonical mechanisms by cytokine receptors suggest their importance and are discussed in this review.
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Jing Wang, Jingjing Li, Lijuan Yin, Tianjie Pu, Jing Wei, Varsha Karthikeyan, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Summary: This study reveals that neuropilin 2 (NRP2) is upregulated in NEPC and plays a role in driving NEPC development and resistance. NRP2 interacts with AR to suppress AR signaling, and activates STAT3 phosphorylation by interacting with VEGFR2, promoting NEPC differentiation and growth.
Article
Multidisciplinary Sciences
Bo Ye, Dandan Fan, Weiwei Xiong, Min Li, Jian Yuan, Qi Jiang, Yuting Zhao, Jianxiang Lin, Jie Liu, Yilv Lv, Xiongjun Wang, Zhigang Li, Jianzhong Su, Yunbo Qiao
Summary: The study identified numerous gained or lost enhancers in ESCC and LNC, contributing to transcriptomic aberrations and revealing putative driver onco-transcription factors. Inhibitors targeting the gained super-enhancers predicted HSP90AA1 and PDE4B as potential therapeutic targets for ESCC. Epigenomic profiling provides insights into reprogrammed cis-regulatory elements during ESCC carcinogenesis and metastasis, offering promising targets for cancer treatment.
NATURE COMMUNICATIONS
(2021)
