The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type.
The altered metabolism of tumors has been considered a target for anticancer therapy. However, the relationship between distinct tumor-initiating lesions and anomalies of tumor metabolism in vivo has not been addressed. We report that MYC-induced mouse liver tumors significantly increase both glucose and glutamine catabolism, whereas MET-induced liver tumors use glucose to produce glutamine. Increased glutamine catabolism in MYC-induced liver tumors is associated with decreased levels of glutamine synthetase (Glul) and the switch from Gls2 to Gls1 glutaminase. In contrast to liver tumors, MYC-induced lung tumors display increased expression of both Glul and Gls1 and accumulate glutamine. We also show that inhibition of Gls1 kills cells that overexpress MYC and catabolize glutamine. Our results suggest that the metabolic profiles of tumors are likely to depend on both the genotype and tissue of origin and have implications regarding the design of therapies targeting tumor metabolism.
G.W. Hooper Research Foundation, University of California, San Francisco, San Francisco, CA 94143, USA. mariia.yuneva@ucsf.edu
Mariia O
MO
Yuneva
Teresa W M
TW
Fan
Thaddeus D
TD
Allen
Richard M
RM
Higashi
Dana V
DV
Ferraris
Takashi
T
Tsukamoto
José M
JM
Matés
Francisco J
FJ
Alonso
Chunmei
C
Wang
Youngho
Y
Seo
Xin
X
Chen
J Michael
JM
Bishop
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000502:physiology; D017931:DNA Primers / Q000235:genetics; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007553:Isotope Labeling; D019344:Lactic Acid / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism*; D055442:Metabolome / Q000235:genetics / Q000502:physiology*; D051379:Mice; D019906:Nuclear Magnetic Resonance, Biomolecular; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
D017931:DNA Primers; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D005973:Glutamine; D019344:Lactic Acid; D005941:Glucokinase; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D005947:Glucose