Tumor cells have an increased demand for nutrients; this demand is met by increased availability of nutrients through vasculogenesis and by enhanced cellular entry of nutrients through upregulation of specific transporters. This review focuses on three groups of nutrient transporters relevant to
cancer:
glucose transporters,
lactate transporters, and
amino acid transporters.
Tumor cells enhance
glucose uptake via induction of GLUT1 and SGLT1, and coordinate the increased entry of
glucose with increased glycolysis. Since enhanced glycolysis in
cancer is associated with
lactate production,
tumor cells must find a way to eliminate
lactic acid to prevent cellular acidification. This is achieved by the upregulation of MCT4, a H+-coupled
lactate transporter. In addition, the Na+-coupled
lactate transporter SMCT1 is silenced in
cancer. SMCT1 also transports
butyrate and
pyruvate, which are inhibitors of
histone deacetylases. The silencing of SMCT1 occurs in
cancers of a variety of tissues. Re-expression of SMCT1 in
cancer cell lines leads to growth arrest and apoptosis in the presence of
butyrate or
pyruvate, suggesting that the transporter may function as a
tumor suppressor.
Tumor cells meet their
amino acid demands by inducing xCT/4F2hc, LAT1/4F2hc, ASCT2, and ATB0,+. xCT/4F2hc is related primarily to
glutathione status, protection against oxidative stress, and cell cycle progression, whereas the other three transporters are related to
amino acid nutrition. Pharmacologic blockade of LAT1/4F2hc, xCT/4F2hc, or ATB0,+ leads to inhibition of
cancer cell growth. Since
tumor cells selectively regulate these nutrient transporters to support their rapid growth, these transporters have potential as
drug targets for
cancer therapy.