mTOR activation in immature cells of primary nasopharyngeal carcinoma and anti-tumor effect of rapamycin in vitro and in vivo.
The mammalian target of rapamycin (mTOR) signaling is a key pathway in the progression of different cancers and in the homeostasis of stem cells. Here, we investigated the link between mTOR signaling and cancer stem cells (CSCs) in nasopharyngeal carcinoma (NPC). We found that human primary NPC expressed embryonic stem cell (ESC) markers: CD133, SOX2 and OCT4 as well as pmTOR and pS6. Primary ESC-positive NPC cells could form secondary NPC in BALB/c nude mice. Rapamycin, an mTOR inhibitor, significantly suppressed ESC-positive NPC cell growth in vitro and tumor formation in vivo. Our findings suggest that mTOR signaling is activated in CSC-like cells and plays an important role in NPC growth.
Department of Otolaryngology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Chunguang
C
Yang
Jianhua
J
Peng
Wenjing
W
Jiang
Yue
Y
Zhang
Xiaoyun
X
Chen
Xianmin
X
Wu
Yi
Y
Zhu
Huxiang
H
Zhang
Jianfu
J
Chen
Jixian
J
Wang
William C S
WC
Cho
Kunlin
K
Jin
D000071916:AC133 Antigen; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000071916:AC133 Antigen; D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D006023:Glycoproteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
Cancer stem cells; Nasopharyngeal carcinoma; Rapamycin; mTOR signaling