Mitochondrial metabolism in cancer stem cells: a therapeutic target for colon cancer.
It has been proposed that the selective elimination of cancer stem cells (CSCs) using targeted therapy could greatly reduce tumor growth, recurrence, and metastasis. To develop effective therapeutic targets for CSC elimination, we aimed to define the properties of CSC mitochondria, and identify CSC-mitochondria- specific targets in colon cancer. We found that colon CSCs utilize mitochondrial oxidative phosphorylation (OXPHOS) to produce ATP. We also found that forkhead box protein 1 (FOXM1)-induced peroxiredoxin 3 (PRDX3) maintains the mitochondrial function, and the FOXM1/PRDX3 mitochondrial pathway maintains survival of colon CSCs. Furthermore, FOXM1 induces CD133 (PROM1/prominin 1) expression, which maintains the stemness of colon CSCs. Together, our findings indicate that FOXM1, PRDX3, and CD133 are potential therapeutic targets for the elimination of CSCs in colon cancer.
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
In-Sung
IS
Song
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Yu Jeong
YJ
Jeong
National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 47392, Korea.
Jin
J
Han
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000628:therapy; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D061105:Peroxiredoxin III / Q000235:genetics / Q000378:metabolism*
D000071916:AC133 Antigen; D015703:Antigens, CD; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III