STAT3-activated CD36 facilitates fatty acid uptake in chronic lymphocytic leukemia cells

Oncotarget
Uri RozovskiZeev Estrov

Abstract

Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA. Because CD36 is oeverexpressed and STAT3 is constitutively activated in CLL cells, we wondered whether STAT3 induces CD36 expression. Sequence analysis identified putative STAT3 binding sites in the CD36 gene promoter. Chromatin immunoprecipitation and an electrophoretic mobility shift assay revealed that STAT3 binds to the CD36 gene promoter. A luciferase assay and STAT3-small hairpin RNA, that significantly decreased the levels of CD36 in CLL cells, established that STAT3 activates the transcription of the CD36 gene. Furthermore, SSO induced a dose-dependent apoptosis of CLL cells. Taken together, our data suggest that STAT3 activates CD36 and that CD36 facilitates FA up...Continue Reading

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Citations

Dec 18, 2018·IUBMB Life·Jean-Marc Zingg
Oct 28, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Uri RozovskiZeev Estrov
Sep 19, 2019·Journal of the National Cancer Institute. Monographs·Etan OrgelSteven D Mittelman
Jul 14, 2019·The Journal of Pharmacology and Experimental Therapeutics·Leslie E LupienPaul W Baures
Jun 27, 2019·British Journal of Haematology·Alfonso E Bencomo-AlvarezAnna M Eiring
Aug 6, 2019·Frontiers in Genetics·Cristina-Mariana NiculiteMihail Eugen Hinescu
Nov 6, 2020·Journal of Toxicology and Environmental Health. Part a·Paige FletcherAndrij Holian
Mar 2, 2019·Nature Reviews. Immunology·David O'SullivanErika L Pearce
Aug 4, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrea AloiaWerner J Kovacs
Dec 1, 2020·Frontiers in Oncology·Martin BöttcherDimitrios Mougiakakos
Mar 16, 2021·Frontiers in Oncology·Borja GuerraLeandro Fernández-Pérez
Nov 2, 2021·Frontiers in Oncology·Yang YuHao Chen
Dec 14, 2021·Experimental Hematology·Lauren A ThurgoodBryone J Kuss

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Methods Mentioned

BETA
flow cytometry
confocal microscopy
ChIP
PCR
transfection
Infection
protein assay
electrophoresis
immunoprecipitation
transfect

Software Mentioned

CellQuest
WinList
TFSEARCH
SevenGo pro
FluoView
GraphPad

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