STAT3-activated CD36 facilitates fatty acid uptake in chronic lymphocytic leukemia cells
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Uri Rozovski1,2, David M. Harris1, Ping Li1, Zhiming Liu1, Preetesh Jain1, Alessandra Ferrajoli1, Jan Burger1, Phillip Thompson1, Nitin Jain1, William Wierda1, Michael J. Keating1 and Zeev Estrov1
1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
2Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Zeev Estrov, email: firstname.lastname@example.org
Keywords: CLL; CD36; metabolism; STAT3
Received: January 31, 2018 Accepted: March 21, 2018 Published: April 20, 2018
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 uptake in CLL cells. Whether CD36 inhibition would provide clinical benefits in CLL remains to be determined.
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