Glucose transporters in cancer metabolism.
OBJECTIVE
Transformed cells exhibit a high rate of glucose consumption beyond that necessary for ATP synthesis. Glucose aids in the generation of biomass and regulates cellular signaling critical for oncogenic progression. A key rate-limiting step in glucose utilization is the transport of glucose across the plasma membrane. This review will highlight key glucose transporters (GLUTs) and current therapies targeting this class of proteins.


RESULTS
GLUTs, enabling the facilitative entry of glucose into a cell, are increasingly found to be deregulated in cancer. Although cancer-specific expression patterns for GLUTs are being identified, comprehensive analyses substantiating a role for individual GLUTs are still required. Studies defining GLUTs as being rate-limiting in specific tumor contexts, the identification of GLUT1 inhibitors via synthetic lethality screens, novel engagement of the insulin-responsive GLUT4 in myeloma and identification of GLUT9 being a urate transporter, are key advances underscoring the need for continued investigation of this large and enigmatic class of proteins.


CONCLUSIONS
Tumor cells exhibit elevated levels of glucose uptake, a phenomenon that has been capitalized upon for the prognostic and diagnostic imaging of a wide range of cancers using radio-labeled glucose analogs. We have, however, not yet been able to target glucose entry in a tumor cell-specific manner for therapy. GLUTs have been identified as rate-limiting in specific tumor contexts. The identification and targeting of tumor-specific GLUTs provide a promising approach to block glucose-regulated metabolism and signaling more comprehensively.
Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Kehinde
K
Adekola
Steven T
ST
Rosen
Mala
M
Shanmugam
D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D050260:Carbohydrate Metabolism; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D000813:Anilides; D000970:Antineoplastic Agents; D051246:Glucose Transport Proteins, Facilitative; D056572:Histone Deacetylase Inhibitors; D011480:Protease Inhibitors; C533793:fasentin; D019833:Genistein