Accumulation of sphingosine kinase 2 protein induces malignant transformation in oral keratinocytes associated with stemness, autophagy, senescence, and proliferation.

Autor: Fugio LB; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Silva G; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Ferraz CL; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Trevisan GL; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Coeli-Lacchini FB; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Garcia CB; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Sousa LO; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Malta TM; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Gil CD; Department of Cell Biology, Federal University of the State of São Paulo, Brazil., Leopoldino AM; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil. Electronic address: andreiaml@usp.br.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2024 Jan; Vol. 1871 (1), pp. 119616. Date of Electronic Publication: 2023 Oct 28.
DOI: 10.1016/j.bbamcr.2023.119616
Abstrakt: Sphingosine-1-phosphate (S1P) signaling has been widely explored as a therapeutic target in cancer. Sphingosine kinase 2 (SK2), one of the kinases that phosphorylate sphingosine, has a cell type and cell location-dependent mechanism of action, so the ability of SK2 to induce cell cycle arrest, apoptosis, proliferation, and survival is strongly influenced by the cell-context. In contrast to SK1, which is widely studied in different types of cancer, including head and neck cancer, the role of SK2 in the development and progression of oral cancer is still poorly understood. In order to elucidate SK2 role in oral cancer, we performed the overexpression of SK2 in non-tumor oral keratinocyte cell (NOK SK2) and in oral squamous cell carcinoma (HN12 SK2), and RNA interference for SK2 in another oral squamous cell carcinoma (HN13 shSK2). In our study we demonstrate for the first time that accumulation of SK2 can be a starting point for oncogenesis and transforms a non-tumor oral keratinocyte (NOK-SI) into highly aggressive tumor cells, even acting on cell plasticity. Furthermore, in oral metastatic cell line (HN12), SK2 contributed even more to the tumorigenesis, inducing proliferation and tumor growth. Our work reveals the intriguing role of SK2 as an oral tumor promoter and regulator of different pathways and cellular processes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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