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Wnt/β-catenin signalling maintains self-renewal and tumourigenicity of head and neck squamous cell carcinoma stem-like cells by activating Oct4
被引:123
作者:
Lee, Sang Hyuk
[1
]
Koo, Bon Seok
[2
]
Kim, Jin Man
[3
]
Huang, Songmei
[3
]
Rho, Young Soo
[4
]
Bae, Woo Jin
[5
]
Kang, Hyun Jung
[6
]
Kim, Young Sook
[6
]
Moon, Jung Hwa
[6
]
Lim, Young Chang
[6
]
机构:
[1] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Otorhinolaryngol Head & Neck Surg, Seoul, South Korea
[2] Chungnam Natl Univ, Dept Otolaryngol Head & Neck Surg, Canc Res Inst, Coll Med, Taejon, South Korea
[3] Chungnam Natl Univ, Dept Pathol, Res Inst Med Sci & Pathol, Coll Med, Taejon, South Korea
[4] Ewha Womans Univ, Dept Otorhinolaryngol Head & Neck Surg, Sch Med, Seoul, South Korea
[5] Hallym Univ, Dept Otolaryngol Head & Neck Surg, Coll Med, Seoul, South Korea
[6] Konkuk Univ, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Res Inst Med Sci, Seoul 143752, South Korea
基金:
新加坡国家研究基金会;
关键词:
head and neck cancer;
cancer stem cells;
Wnt/beta-catenin signalling;
Oct4;
target therapy;
CANCER CELLS;
DRUG-RESISTANCE;
BLADDER-CANCER;
BETA-CATENIN;
EXPRESSION;
MARKER;
KERATINOCYTES;
PROGRESSION;
PATHWAY;
SKIN;
D O I:
10.1002/path.4383
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Accumulating evidence suggests that a distinct subpopulation of cancer stem cells (CSCs) is responsible for tumour initiation and progression in head and neck squamous cell carcinoma (HNSCC). Wnt/beta-catenin signalling is essential for stem cell regulation and tumourigenesis, but its molecular mechanism in HNSCC CSCs remains unknown. We investigated whether Wnt/beta-catenin signalling regulates self-renewal and tumourigenicity of HNSCC stem-like cells in vitro and in vivo. Cytoplasmic/nuclear beta-catenin, a major effector of Wnt/beta-catenin signalling, was expressed in a subpopulation of tumour cells in primary HNSCC tissue but in none of normal head and neck tissues. Overexpression of beta-catenin increased proliferation of HNSCC cells and induced dedifferentiation of these cells to cells with stem-like features. Knockdown of beta-catenin in HNSCC stem-like cells blocked their self-renewal capacity, stemness-associated gene expression, chemoresistance, and in vivo tumourigenicity. Furthermore, beta-catenin directly regulates Oct4 transcription in HNSCC stem-like cells. In addition, the effect of shRNA-mediated repression of beta-catenin on CSC traits in HNSCC stem-like cells was reversed by overexpression of Oct4. In patients with HNSCC, higher levels of both cytoplasmic/nuclear beta-catenin and Oct4 correlated with the worst prognosis. These results suggest inhibition of Wnt/beta-catenin signalling as a novel therapeutic strategy for targeting HNSCC stem-like cells. Copyright (C) 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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页码:99 / 107
页数:9
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