mTOR plays critical roles in pancreatic cancer stem cells through specific and stemness-related functions.
Pancreatic cancer is characterized by near-universal mutations in KRAS. The mammalian target of rapamycin (mTOR), which functions downstream of RAS, has divergent effects on stem cells. In the present study, we investigated the significance of the mTOR pathway in maintaining the properties of pancreatic cancer stem cells. The mTOR inhibitor, rapamycin, reduced the viability of CD133(+) pancreatic cancer cells and sphere formation which is an index of self-renewal of stem-like cells, indicating that the mTOR pathway functions to maintain cancer stem-like cells. Further, rapamycin had different effects on CD133(+) cells compared to cyclopamine which is an inhibitor of the Hedgehog pathway. Thus, the mTOR pathway has a distinct role although both pathways maintain pancreatic cancer stem cells. Therefore, mTOR might be a promising target to eliminate pancreatic cancer stem cells.
Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Sakuragaoka, Kagoshima, 890-8520, Japan.
Shyuichiro
S
Matsubara
Qiang
Q
Ding
Yumi
Y
Miyazaki
Taisaku
T
Kuwahata
Koichiro
K
Tsukasa
Sonshin
S
Takao
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; D053823:Hedgehog Proteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D014704:Veratrum Alkaloids; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; C000541:cyclopamine