Metabolic rewiring in melanoma.
Oncogene-driven metabolic rewiring is an adaptation to low nutrient and oxygen conditions in the tumor microenvironment that enables cancer cells of diverse origin to hyperproliferate. Aerobic glycolysis and enhanced reliance on glutamine utilization are prime examples of such rewiring. However, tissue of origin as well as specific genetic and epigenetic changes determines gene expression profiles underlying these metabolic alterations in specific cancers. In melanoma, activation of the mitogen-activated protein kinase (MAPK) pathway driven by mutant BRAF or NRAS is a primary cause of malignant transformation. Activity of the MAPK pathway, as well as other factors, such as HIF1α, Myc and MITF, are among those that control the balance between non-oxidative and oxidative branches of central carbon metabolism. Here, we discuss the nature of metabolic alterations that underlie melanoma development and affect its response to therapy.
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA.
B I
BI
Ratnikov
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA.
D A
DA
Scott
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA.
A L
AL
Osterman
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA.
J W
JW
Smith
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla CA, USA.
Z A
ZA
Ronai
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044127:Epigenesis, Genetic; D020558:GTP Phosphohydrolases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents; D008565:Membrane Proteins; D005973:Glutamine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human