Aberrant LPL Expression, Driven by STAT3, Mediates Free Fatty Acid Metabolism in CLL Cells

Molecular Cancer Research : MCR
Uri RozovskiZeev Estrov

Abstract

While reviewing chronic lymphocytic leukemia (CLL) bone marrow slides, we identified cytoplasmic lipid vacuoles in CLL cells but not in normal B cells. Because lipoprotein lipase (LPL), which catalyzes hydrolysis of triglycerides into free fatty acids (FFA), is aberrantly expressed in CLL, we investigated whether LPL regulates the oxidative metabolic capacity of CLL cells. We found that unlike normal B cells, CLL cells metabolize FFAs. Because STAT3 is constitutively activated in CLL cells and because we identified putative STAT3 binding sites in the LPL promoter, we sought to determine whether STAT3 drives the aberrant expression of LPL. Transfection of luciferase reporter gene constructs driven by LPL promoter fragments into MM1 cells revealed that STAT3 activates the LPL promoter. In addition, chromatin immunoprecipitation confirmed that STAT3 binds to the LPL promoter. Furthermore, transfection of CLL cells with STAT3-shRNA downregulated LPL transcripts and protein levels, confirming that STAT3 activates the LPL gene. Finally, transfection of CLL cells with LPL-siRNAs decreased the capacity of CLL cells to oxidize FFAs and reduced cell viability. Our study suggests that CLL cells adopt their metabolism to oxidize FFA. Activ...Continue Reading

References

Feb 21, 1998·Nucleic Acids Research·T HeinemeyerN A Kolchanov
Jun 1, 2002·Science·David S Aaronson, Curt M Horvath
Nov 9, 2002·Proceedings of the National Academy of Sciences of the United States of America·R A NeeseM K Hellerstein
Nov 28, 2002·Journal of Lipid Research·Martin MerkelIra J Goldberg
Dec 17, 2002·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·James R MeadDipak P Ramji
Jan 9, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stuart G TangyePhilip D Hodgkin
Feb 25, 2005·The New England Journal of Medicine·Nicholas ChiorazziManlio Ferrarini
Apr 2, 2005·Blood·Pablo OppezzoUNKNOWN French Cooperative Group on CLL
May 29, 2007·Breast Cancer Research : BCR·Marjan BerishajJacqueline F Bromberg
Aug 21, 2007·Best Practice & Research. Clinical Haematology·Nicholas Chiorazzi
Nov 1, 2007·Nutrition & Metabolism·Amanda M Gonzales, Robert A Orlando
Apr 28, 2010·Journal of Lipid Research·Maxwell A RubyRonald M Krauss
Oct 12, 2010·PPAR Research·Maryam RakhshandehrooSander Kersten
Jan 25, 2011·Nature Reviews. Cancer·Rob A CairnsTak W Mak
Mar 3, 2011·Molecular Cancer Research : MCR·Zhiming LiuZeev Estrov
Jul 31, 2012·International Journal of Oncology·Xiaochun WangJia-Lin Yang
Nov 20, 2012·Leukemia·D E SpanerR Gorzcynski
Mar 1, 2013·Nature Reviews. Cancer·Arkaitz CarracedoPier Paolo Pandolfi
Apr 26, 2013·Leukemia & Lymphoma·Cecilia AbreuPablo Oppezzo

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Citations

Dec 9, 2015·Leukemia & Lymphoma·Uri RozovskiZeev Estrov
Feb 5, 2016·Journal of Cellular Physiology·William B KinlawNancy B Kuemmerle
Nov 13, 2015·European Journal of Haematology·Louise KristensenMichael Boe Møller
Jun 7, 2016·Liver International : Official Journal of the International Association for the Study of the Liver·Dan CaoDiego F Calvisi
Aug 10, 2016·European Journal of Haematology·Ans RomboutJan Philippé
Oct 21, 2016·Pathology Oncology Research : POR·Zoltán MátraiTamás Masszi
Feb 3, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yan XuLi Zhu
Feb 22, 2018·Leukemia & Lymphoma·Uri RozovskiZeev Estrov
Feb 5, 2019·Cellular and Molecular Life Sciences : CMLS·Azin SamimiNajmaldin Saki
Jan 19, 2019·British Journal of Haematology·Lauren A ThurgoodBryone J Kuss
Oct 28, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Uri RozovskiZeev Estrov
Sep 27, 2018·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Hoda Soleymani AbyanehRaymond Lai
Dec 6, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel Prieto, Pablo Oppezzo
Jul 20, 2017·International Journal of Cancer. Journal International Du Cancer·Uri RozovskiZeev Estrov
Oct 16, 2018·Frontiers in Cell and Developmental Biology·Angela IannicielloG Vignir Helgason
Oct 1, 2016·Hepatic Oncology·Mingda WangTian Yang
Jul 14, 2019·The Journal of Pharmacology and Experimental Therapeutics·Leslie E LupienPaul W Baures
Aug 29, 2019·International Journal of Molecular Sciences·Anna C Beielstein, Christian P Pallasch
Jan 29, 2017·Molecular Cancer Research : MCR·Uri RozovskiZeev Estrov
Dec 1, 2020·Frontiers in Oncology·Martin BöttcherDimitrios Mougiakakos
Apr 30, 2021·Frontiers in Cell and Developmental Biology·Jiayi XieMeng Zhao
Aug 28, 2021·International Journal of Molecular Sciences·Ioanna E Stergiou, Efstathia K Kapsogeorgou
Dec 14, 2021·Experimental Hematology·Lauren A ThurgoodBryone J Kuss

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