The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.

Autor: Alkafaas SS; Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt. samar.alkafas@science.tanta.edu.eg., Elsalahaty MI; Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt. mohamed.elsalahaty@science.tanta.edu.eg., Ismail DF; Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Radwan MA; Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt., Elkafas SS; Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Menofia, Egypt.; Faculty of Control System and Robotics, ITMO University, Saint-Petersburg, 197101, Russia., Loutfy SA; Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.; Nanotechnology Research Center, British University, Cairo, Egypt., Elshazli RM; Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University-Egypt, New Damietta, 34517, Egypt., Baazaoui N; Biology Department, College of Sciences and Arts Muhayil Assir, King Khalid University, Abha 61421, Saudi Arabia., Ahmed AE; Biology Department, College of Science, King Khalid University, Abha 61413, Saudi Arabia., Hafez W; NMC Royal Hospital, 16th Street, 35233, Khalifa, Abu Dhabi, United Arab Emirates.; Medical Research Division, Department of Internal Medicine, The National Research Centre, Cairo 11511, Egypt., Diab M; Burjeel Hospital Abu Dhabi, Abu Dhabi, United Arab Emirates., Sakran M; Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt.; Biochemistry Department, Faculty of Science, University of Tabuk, Tabuk 47512, Saudi Arabia., El-Saadony MT; Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt., El-Tarabily KA; Department of Biology, College of Science, United Arab Emirates University, Al-Ain 15551, United Arab Emirates., Kamal HK; Anatomy and Histology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Hessien M; Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2024 Feb 28; Vol. 24 (1), pp. 89. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1186/s12935-024-03221-8
Abstrakt: Cancer chemoresistance is a problematic dilemma that significantly restrains numerous cancer management protocols. It can promote cancer recurrence, spreading of cancer, and finally, mortality. Accordingly, enhancing the responsiveness of cancer cells towards chemotherapies could be a vital approach to overcoming cancer chemoresistance. Tumour cells express a high level of sphingosine kinase-1 (SphK1), which acts as a protooncogenic factor and is responsible for the synthesis of sphingosine-1 phosphate (S1P). S1P is released through a Human ATP-binding cassette (ABC) transporter to interact with other phosphosphingolipids components in the interstitial fluid in the tumor microenvironment (TME), provoking communication, progression, invasion, and tumor metastasis. Also, S1P is associated with several impacts, including anti-apoptotic behavior, metastasis, mesenchymal transition (EMT), angiogenesis, and chemotherapy resistance. Recent reports addressed high levels of S1P in several carcinomas, including ovarian, prostate, colorectal, breast, and HCC. Therefore, targeting the S1P/SphK signaling pathway is an emerging therapeutic approach to efficiently attenuate chemoresistance. In this review, we comprehensively discussed S1P functions, metabolism, transport, and signaling. Also, through a bioinformatic framework, we pointed out the alterations of SphK1 gene expression within different cancers with their impact on patient survival, and we demonstrated the protein-protein network of SphK1, elaborating its sparse roles. Furthermore, we made emphasis on different machineries of cancer resistance and the tight link with S1P. We evaluated all publicly available SphK1 inhibitors and their inhibition activity using molecular docking and how SphK1 inhibitors reduce the production of S1P and might reduce chemoresistance, an approach that might be vital in the course of cancer treatment and prognosis.
(© 2024. The Author(s).)
Databáze: MEDLINE
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