Accéder au contenu
Merck

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

Molecular cancer research : MCR (2015-03-04)
Uri Rozovski, Srdana Grgurevic, Carlos Bueso-Ramos, David M Harris, Ping Li, Zhiming Liu, Ji Yuan Wu, Preetesh Jain, William Wierda, Jan Burger, Susan O'Brien, Nitin Jain, Alessandra Ferrajoli, Michael J Keating, Zeev Estrov
RÉSUMÉ

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. Activated STAT3 induces LPL, which catalyzes the hydrolysis of triglycerides into FFA. Therefore, inhibition of STAT3 is likely to prevent the capacity of CLL cells to utilize FFA.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
Acide oléique, technical grade, 90%
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
Acide palmitique, ≥99%
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
1,2-propanediol, ≥99.5% (GC), FCC, FG
Sigma-Aldrich
Acide oléique, BioReagent, suitable for cell culture
SAFC
L-Glutamine
Sigma-Aldrich
Acide oléique, ≥99% (GC)
Sigma-Aldrich
1,2-propanediol, ACS reagent, ≥99.5%
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Hematoxylin
Sigma-Aldrich
Acide palmitique, BioXtra, ≥99%
Sigma-Aldrich
Acide oléique, meets analytical specification of Ph, Eur., 65.0-88.0% (GC)
Sigma-Aldrich
Acide oléique, natural, FCC
Sigma-Aldrich
Propylène glycol, meets USP testing specifications
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Hematoxylin, certified by the Biological Stain Commission
Sigma-Aldrich
1,2-propanediol, ReagentPlus®, 99%
Sigma-Aldrich
Acide palmitique, ≥98%, FCC, FG
Sigma-Aldrich
Acide palmitique, ≥98% palmitic acid basis (GC)
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
1,2-propanediol, puriss. p.a., ACS reagent, ≥99.5% (GC)
Sigma-Aldrich
Acide palmitique, natural, 98%, FG
Sigma-Aldrich
1,2-propanediol, meets analytical specification of Ph. Eur., BP, USP, ≥99.5%
Sigma-Aldrich
MISSION® esiRNA, targeting human LCP1
Sigma-Aldrich
MISSION® esiRNA, targeting human LPL
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Lcp1
Sigma-Aldrich
MISSION® esiRNA, targeting mouse Lpl