TY - JOUR
T1 - Fatty acid metabolism in aggressive B-cell lymphoma is inhibited by tetraspanin CD37
AU - Peeters, Rens
AU - Cuenca-Escalona, Jorge
AU - Zaal, Esther A.
AU - Hoekstra, Anna T.
AU - Balvert, Anouk C.G.
AU - Vidal-Manrique, Marcos
AU - Blomberg, Niek
AU - van Deventer, Sjoerd J.
AU - Stienstra, Rinke
AU - Jellusova, Julia
AU - Giera, Martin
AU - Hannibal, Luciana
AU - Spiekerkoetter, Ute
AU - ter Beest, Martin
AU - Berkers, Celia R.
AU - van Spriel, Annemiek B.
PY - 2022/9/13
Y1 - 2022/9/13
N2 - The importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic marker for aggressive B-cell lymphoma, as essential membrane-localized inhibitor of FA metabolism. Deletion of CD37 on lymphoma cells results in increased FA oxidation shown by functional assays and metabolomics. Furthermore, CD37-negative lymphomas selectively deplete palmitate from serum in mouse studies. Mechanistically, CD37 inhibits the FA transporter FATP1 through molecular interaction. Consequently, deletion of CD37 induces uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation, and inhibition of FATP1 reverses this phenotype. Large lipid deposits and intracellular lipid droplets are observed in CD37-negative lymphoma tissues of patients. Moreover, inhibition of carnitine palmitoyl transferase 1 A significantly compromises viability and proliferation of CD37-deficient lymphomas. Collectively, our results identify CD37 as a direct gatekeeper of the FA metabolic switch in aggressive B-cell lymphoma.
AB - The importance of fatty acid (FA) metabolism in cancer is well-established, yet the mechanisms underlying metabolic reprogramming remain elusive. Here, we identify tetraspanin CD37, a prognostic marker for aggressive B-cell lymphoma, as essential membrane-localized inhibitor of FA metabolism. Deletion of CD37 on lymphoma cells results in increased FA oxidation shown by functional assays and metabolomics. Furthermore, CD37-negative lymphomas selectively deplete palmitate from serum in mouse studies. Mechanistically, CD37 inhibits the FA transporter FATP1 through molecular interaction. Consequently, deletion of CD37 induces uptake and processing of exogenous palmitate into energy and essential building blocks for proliferation, and inhibition of FATP1 reverses this phenotype. Large lipid deposits and intracellular lipid droplets are observed in CD37-negative lymphoma tissues of patients. Moreover, inhibition of carnitine palmitoyl transferase 1 A significantly compromises viability and proliferation of CD37-deficient lymphomas. Collectively, our results identify CD37 as a direct gatekeeper of the FA metabolic switch in aggressive B-cell lymphoma.
U2 - 10.1038/s41467-022-33138-7
DO - 10.1038/s41467-022-33138-7
M3 - Article
C2 - 36100608
AN - SCOPUS:85137810420
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 5371
ER -
