Review
Biochemistry & Molecular Biology
Longfei Deng, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: TRAIL holds therapeutic potential in cancer treatment, but many cancers, including GBM, exhibit resistance. Recent studies have identified new mechanisms in regulating TRAIL-induced apoptosis in GBM and effective combinatorial strategies. The TRAIL/TRAIL death receptor axis may have future clinical applications for GBM treatment.
Article
Medicine, General & Internal
Liu Shi, Yu Xiong, Xiaoyan Hu, Zhihao Wang, Conghua Xie
Summary: In this study, it was found that inhibition of BRD4 or genetic knock-down of BRD4 can increase the sensitivity of lung cancer cells to TRAIL, and this sensitization is not related to death receptors DR4 and DR5. The results suggest that a combination therapy with TRAIL and BRD4 inhibitors may be a promising strategy to overcome TRAIL resistance in NSCLC.
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Koki Tachibana, Kohshi Kusumoto, Mai Ogawa, Hidenori Ando, Taro Shimizu, Yu Ishima, Tatsuhiro Ishida, Keiichiro Okuhira
Summary: Formation of foam cells in atherosclerosis is caused by excessive lipid accumulation by macrophages. FTY720 has been shown to inhibit atherosclerotic plaque development, and this study reveals that FTY720 induces ABCA1 expression through SphK2-mediated acetylation of H3K9, leading to suppression of lipid accumulation in macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Molly Congdon, Russell G. Fritzemeier, Yugesh Kharel, Anne M. Brown, Vlad Serbulea, David R. Bevan, Kevin R. Lynch, Webster L. Santos
Summary: Elevated levels of Sphingosine 1-phosphate (S1P) and increased expression of Sphingosine kinase iso-forms (SphK1 and SphK2) are associated with various disease states. The development of selective inhibitors for SphK1 and SphK2 has become a focus of drug discovery, with studies focusing on optimizing binding in the SphK2 substrate binding site. The identification of indole-based compounds with 1,5-disubstitution as potent inhibitors highlights the potential for targeting SphK2 with improved potency and selectivity.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Gulibositan Aji, Sheng Jiang, Halmurat Obulkasim, Zhiqiang Lu, Wei Wang, Pu Xia
Summary: This study reveals that SphK2 regulates the trafficking of insulin receptor (InsR) by affecting the endocytosis and recycling of InsR, thus modulating insulin signaling. These findings provide mechanistic evidence for SphK2 as a potential intervention target for insulin resistance and type 2 diabetes (T2D).
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
You-Take Oh, Shi-Yong Sun
Summary: The involvement of the TRAIL/death receptor signaling pathway in the regulation of cancer invasion and metastasis is complex, with both positive and negative roles reported. The underlying molecular mechanisms are even more complicated. This review focuses on discussing the current understanding of how TRAIL/death receptor-mediated signaling regulates cancer cell invasion and metastasis.
Review
Biochemistry & Molecular Biology
Ling-Wei Hii, Felicia Fei-Lei Chung, Chun-Wai Mai, Pei Yuen Ng, Chee-Onn Leong
Summary: SPHK1 is a conserved lipid enzyme that catalyzes the formation of S1P, and has been implicated in oncogenic functions, particularly in breast cancer. Recent evidence suggests a role for SPHK1 in regulating CSCs, indicating the therapeutic potential of targeting SPHK1 in refractory cancers enriched with CSCs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Hao Li, Christopher D. Sibley, Yugesh Kharel, Tao Huang, Anne M. Brown, Laura G. Wonilowicz, David R. Bevan, Kevin R. Lynch, Webster L. Santos
Summary: The study focused on the structure-activity relationship profiling of 2-(hydroxymethyl)pyrrolidine-based inhibitors, identifying 22d as the most potent dual SphK1/SphK2 inhibitor. Molecular modeling studies showed essential hydrogen bonding interactions between 22d and SphK1 and SphK2, providing insight into the intermolecular interactions in the active sites for maximal dual inhibitory activity.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Rocio Diaz Escarcega, Louise D. McCullough, Andrey S. Tsvetkov
Summary: S1P, a bioactive lipid molecule synthesized by SPHK1 and SPHK2, plays key roles in various signaling pathways, with SPHK2 regulating processes in the nucleus and mitochondria. Investigation into SPHK2 as a target for age-associated conditions is ongoing.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yanyan Wang, Yun-Ling Tai, Grayson Way, Jing Zeng, Derrick Zhao, Lianyong Su, Xixian Jiang, Kaitlyn G. Jackson, Xuan Wang, Emily C. Gurley, Jinze Liu, Jinpeng Liu, Weidong Chen, Xiang-Yang Wang, Arun J. Sanyal, Phillip B. Hylemon, Huiping Zhou
Summary: This study investigated the role of hepatocyte-specific HuR in regulating hepatic lipid metabolism and found that HuR deficiency leads to increased hepatic lipid accumulation, inflammation, disrupted bile acid homeostasis, and enhanced liver fibrosis. Additionally, HuR was identified as a repressor of H19 expression, and the downregulation of H19 alleviated NAFLD in mice with HuR deficiency.
CELL AND BIOSCIENCE
(2022)
Article
Neurosciences
Huitong Song, Holly P. McEwen, Thomas Duncan, Jun Yup Lee, Jonathan D. Teo, Anthony S. Don
Summary: SphK2 deficiency leads to decreased remyelination and maintenance of myelin with aging, possibly due to elevated levels of cytotoxic sphingosine and ceramide.
Review
Oncology
Hojjat Alizadeh Zeinabad, Eva Szegezdi
Summary: TRAIL, as a promising anticancer drug with low toxicity, has not been successfully translated into a therapeutic molecule due to its short in vivo half-life and tumor cells' resistance. Nanotechnology shows potential to overcome these limitations and offers better solutions.
Article
Medicine, Research & Experimental
Hui Yan, Hu Zhao, Shao-wei Yi, Hang Zhuang, Dao-wen Wang, Jian-gang Jiang, Gui-fen Shen
Summary: The objective of this study was to investigate whether sphingosine-1-phosphate (S1P) could prevent cardiac remodeling and the associated mechanisms. The results demonstrated that S1P treatment improved cardiac function and reduced cardiac fibrosis in a mouse model of transverse aortic constriction (TAC). The study also identified sphingosine kinase 2 (SphK2) and the S1P receptor 2 (S1PR2)/extracellular regulated protein kinases (ERK) pathway as potential mediators of the anti-remodeling effect of S1P on the heart.
CURRENT MEDICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Rosaria Bassi, Stefania Brambilla, Cristina Tringali, Paola Giussani
Summary: The study found that GBM cells overexpressing EGFR have higher levels of S1P and increased SK1 activity, leading to resistance to the standard chemotherapeutic drug temozolomide. This suggests a functional link between EGFR and S1P signaling pathways in enhancing the survival properties of GBM cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
