@conference{
author = "Mandić, Miloš and Misirkić Marjanović, Maja and Vučićević, Ljubica and Bošnjak, Mihajlo and Perović, Vladimir and Ristić, Biljana and Ćirić, Darko and Janjetović, Kristina and Paunović, Verica and Stevanović, Danijela and Kosić, Milica and Harhaji-Trajković, Ljubica and Trajković, Vladimir",
year = "2023",
abstract = "Introduction: Autophagy has been shown to participate in the differentiation of hematopoietic and
leukemic cells. We investigated the mechanisms of autophagy action in the differentiation induced by
PKC activator phorbol myristate acetate (PMA) in HL-60 acute myeloid leukemia cells.
Methods: The macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8 were assessed by
flow cytometry and RT-qPCR. Autophagy was monitored by RT-qPCR analysis of autophagy-related (ATG)
gene expression, LC3-II/p62 immunoblotting, beclin-1/Bcl-2 interaction, nuclear translocation of TFEB
and FOXO1/3. The activation of MAP kinases, ERK and JNK was assessed by immunoblotting. Pharmacological inhibition and RNA interference were used to determine the role of MAP kinases and autophagy
in HL60 cell differentiation.
Results: PMA-triggered differentiation of HL-60 cells into macrophage-like cells was confirmed by elevated expression of macrophage markers CD11b, CD13, CD14, CD45, EGR1, CSF1R, and IL-8. The induction of autophagy was demonstrated by accumulation/punctuation of LC3-II, and the increase in
autophagic flux. PMA also increased nuclear translocation of TFEB, FOXO1/3, as well asthe expression of
several ATG genesin HL-60 cells. PMA stimulated the phosphorylation of ERK and JNK via PKC-dependent
mechanism. Pharmacological or genetic inhibition of ERK or JNK suppressed PMA-triggered nuclear
translocation of TFEB and FOXO1/3, ATG expression, dissociation of beclin-1 from Bcl-2, autophagy induction, and differentiation of HL-60 cells into macrophage-like cells.
Conclusion: Our study revealed the involvement of ERK and JNK in TFEB/FOXO-dependent autophagy
and differentiation of HL60 cells, indicating MAP kinase-mediated autophagy as a possible target in differentiation therapy of AML.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "MAP kinases activate TFEB/FOXO-dependent autophagy involved in phorbol myristate acetate-induced macrophage differentiation of HL-60 leukemia cells",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6285"
}
