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)
Review
Oncology
Saida Mebarek, Najwa Skafi, Leyre Brizuela
Summary: Prostate cancer is the second most common cancer in men worldwide, with the majority of patients being above 65. Sphingosine 1-phosphate (S1P) is a bioactive lipid that plays a crucial role in the oncogenesis of prostate cancer. S1P metabolism and its enzymes have been extensively studied in relation to prostate cancer development and potential therapeutic targets. This review summarizes the significant findings and the current progress in targeting S1P metabolism for prostate cancer treatment.
Review
Oncology
Preeti Gupta, Aaliya Taiyab, Afzal Hussain, Mohamed F. Alajmi, Asimul Islam, Md. Imtaiyaz Hassan
Summary: Cancer is a leading cause of global mortality, with SphK1 and its metabolite S1P being potential therapeutic targets due to their over-expression in various cancers and metabolic disorders. This review discusses the sphingolipid metabolism and the role of SphK isoforms in human malignancies, as well as the potential of SphK inhibitors in cancer therapy. It highlights the importance of sphingolipid metabolites in regulating physiological processes and the significance of the SphK/S1P signaling axis in human pathologies.
Article
Biochemistry & Molecular Biology
Jean-Philip Truman, Christian F. Ruiz, Magali Trayssac, Cungui Mao, Yusuf A. Hannun, Lina M. Obeid
Summary: This study reveals that under conditions of serine starvation, SK1 is degraded in a p53-independent manner, requiring the action of the proteasome. Overexpression of SK1 to compensate for its loss is detrimental to cell growth under serine deprivation, indicating that suppression of SK1 under these conditions is adaptive. The effects of SK1 suppression on intracellular reactive oxygen species were mimicked by D-erythro-sphingosine, suggesting that the accumulation of its substrate, sphingosine, is responsible for these effects.
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)
Article
Biochemistry & Molecular Biology
Fabiola N. Velazquez, Jeffrey L. Stith, Leiqing Zhang, Amira M. Allam, John Haley, Lina M. Obeid, Ashley J. Snider, Yusuf A. Hannun
Summary: This study suggests that targeting sphingosine kinase 1 (SK1), a key enzyme upregulated in various types of cancer, can effectively decrease tumor growth in lymphoma without functional p53. This positions SK1 as a potential therapeutic target for tumors that lack functional p53.
Article
Biochemistry & Molecular Biology
Ilma Shakeel, Shama Khan, Sonam Roy, Fakhir Sherwani, Sheikh F. Ahmad, Sukhwinder Singh Sohal, Mohammad Afzal, Md Imtaiyaz Hassan
Summary: The signaling of SphK1 and S1P regulates various diseases, and this study explores the inhibitory potential and binding affinity of SphK1 with CA, SA, and MF. The compounds bind to SphK1 with high affinity and inhibit its kinase activity. These findings suggest the potential of designing novel anti-cancer therapeutics by targeting SphK1.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Su Bin Kim, Yoon Sin Oh, Kwang Joon Kim, Sung Woo Cho, Seung Ki Park, Dong Jae Baek, Eun-Young Park
Summary: This study found that the tail structure of PF-543 influences its metabolic stability. Compounds with aliphatic tails have high inhibitory effects on pancreatic cancer cells but slightly lower selectivity for SK1.
Review
Biochemistry & Molecular Biology
Na Wang, Jing-Yi Li, Bo Zeng, Gui-Lan Chen
Summary: Sphingosine-1-phosphate (S1P) is a crucial sphingolipid molecule that regulates cardiovascular functions through binding and activating multiple G protein-coupled receptors in different cell types. It affects cell proliferation, migration, differentiation, and apoptosis through various downstream signaling pathways. Abnormal S1P levels are associated with cardiovascular disorders, and further research is needed to explore the potential therapeutic use of S1P in these diseases.
Review
Virology
Lu Zhang, Juan Liu, Erya Xiao, Qingzhen Han, Lin Wang
Summary: Viruses can create a unique cellular environment that facilitates replication and transmission. The SphK/S1P axis plays a crucial role in regulating cellular activities during viral infections. Depending on the type of virus, the SphK/S1P axis can have pro- or anti-viral activities through the host immune system or intracellular signaling pathways and cell proliferation.
REVIEWS IN MEDICAL VIROLOGY
(2023)
Article
Endocrinology & Metabolism
David Montefusco, Maryam Jamil, Melissa A. Maczis, William Schroeder, Moshe Levi, Suman Ranjit, Jeremy Allegood, Dipankar Bandyopadhyay, Reuben Retnam, Sarah Spiegel, L. Ashley Cowart
Summary: Men with NAFLD are more likely to progress to NASH and liver fibrosis than women. This study revealed a novel pathway involving estrogen-mediated cross-talk between hepatocytes and HSCs that may contribute to sex differences in NAFLD through the anti-fibrogenic function of the S1P/S1PR3 axis.
MOLECULAR METABOLISM
(2022)
Letter
Oncology
Chen Wang, Taiyang Ye, Wenjing Wang, Keqi Song, Jie Zhu, Lan Dai, Wen Di
Summary: In this study, it was found that SphK1 is over-expressed in omental metastases of EOC patients. The inhibition of SphK1 suppressed the metastatic ability of EOC induced by adipocytes. SphK1 modulates adipocyte-induced E/N-cadherin switch through Twist1, suggesting a new target for EOC therapy.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Olga A. Sukocheva, Dong Gui Hu, Robyn Meech, Anupam Bishayee
Summary: Breast cancer MCF-7 cell-line-derived mammospheres exhibit enriched CD44+/CD24- cells resembling breast cancer stem cells, expressing high levels of S1P3. Growth-promoting agents induce SphK1 and S1P3 translocation to the nucleus, while TNF alpha inhibits their nuclear translocation and promotes apoptosis in mammospheres. The study suggests inhibiting SphK1 and S1P3 nuclear translocation as a novel approach to prevent BCSC proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Joseph L. Wilkerson, Sandip K. Basu, Megan A. Stiles, Amanda Prislovsky, Richard C. Grambergs, Sarah E. Nicholas, Dimitrios Karamichos, Jeremy C. Allegood, Richard L. Proia, Nawajes Mandal
Summary: The role of sphingosine kinase 1 (SphK1) in corneal neovascularization (NV) was investigated. The study showed that ablation of SphK1 can significantly reduce NV invasion in the cornea following injury. Furthermore, sphingolipid analysis revealed lower levels in Sphk1(-/-) corneas after injury.
Article
Dentistry, Oral Surgery & Medicine
Nader Hamdan, Anjali Y. Bhagirath, Eraldo L. Batista
Summary: This study evaluated the changes in Sphingosine-1-Phosphate (S1P) levels and Sphingosine Kinase (SPHK) activity in response to non-surgical periodontal treatment. The results showed that non-surgical treatment led to a decrease in SPHK activity and S1P levels, which correlated with improvements in periodontal parameters. Specifically, SPHK1 levels significantly decreased after periodontal treatment.
