RRC ID 72646
Author Minematsu H, Afify SM, Sugihara Y, Hassan G, Zahra MH, Seno A, Adachi M, Seno M.
Title Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis.
Journal Sci Rep
Abstract Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis.
Volume 12(1)
Pages 15628
Published 2022-9-17
DOI 10.1038/s41598-022-19265-7
PII 10.1038/s41598-022-19265-7
PMID 36115905
PMC PMC9482612
MeSH Animals Arachidonic Acid / metabolism Culture Media, Conditioned / pharmacology Dinoprostone* / metabolism Dinoprostone* / pharmacology Mice Neoplasms* / metabolism Neoplastic Stem Cells / metabolism Phosphatidylinositol 3-Kinases / metabolism Protein-Tyrosine Kinases / metabolism Proto-Oncogene Proteins c-akt / metabolism Signal Transduction
IF 3.998
Human and Animal Cells iPS-MEF-Ng-20D-17(APS0001)