Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer             stem-like side population cells.
The cancer stem cell (CSC) is responsible for the initiation, proliferation             and radiation resistance. Side population (SP) cells are a rare subset of cells             enriched with CSCs. The targeting of key signaling pathways that are active in             CSCs is a therapeutic approach to treating cancer. Notch signaling is important             for the self-renewal and maintenance of stem cells. Our previous studies demonstrated             that downregulation of Notch signaling could enhance radiosensitivity of nasopharyngeal             carcinoma (NPC) cells. In this study, we found that Notch signaling was highly             activated in SP cells compared with that of non-SP (NSP) cells of NPC. Therefore,             Notch inhibition could reduce the proportion of SP cells. As SP cells decreased,             proliferation, anti-apoptosis and tumorigenesis were also decreased. This study             shows that Notch inhibition may be a promising clinical approach in CSC-targeting             therapy for NPC.
Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai 200040, PR China.
Shudong
S
Yu
Ruxin
R
Zhang
Fenye
F
Liu
Hong
H
Wang
Jing
J
Wu
Yanqing
Y
Wang
D000818:Animals; D002277:Carcinoma; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058985:Side-Population Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
D004151:Dipeptides; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D051880:Receptors, Notch