Potential role of Notch1 signaling pathway in laryngeal squamous cell carcinoma cell line Hep-2 involving proliferation inhibition, cell cycle arrest, cell apoptosis, and cell migration

被引:21
作者
Jiao, Jing [1 ,2 ]
Qin, Zhaobing [1 ]
Li, Sha [3 ]
Liu, Hongtao [4 ]
Lu, Zhaoming [4 ]
机构
[1] Zhengzhou Univ, Dept Otorhinolaryngol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
[2] Zhengzhou Hosp, Dept Stomatol, Zhengzhou 450003, Henan, Peoples R China
[3] Zhengzhou Univ, Dept Stomatol, Affiliated Hosp 1, Zhengzhou 450052, Henan, Peoples R China
[4] Zhengzhou Univ, Cell Biol Lab, Dept Bioengn, Zhengzhou 450001, Henan, Peoples R China
关键词
Notch1 signaling pathway; laryngeal carcinoma cell Hep-2; cell cycle; cell apoptosis; invasion and metastasis; HUMAN BREAST-CANCER; GENE AMPLIFICATION; METASTASIS; P53; OVEREXPRESSION; PROGRESSION; ACTIVATION; EXPRESSION; MOTILITY; INVASION;
D O I
10.3892/or_00000504
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Head and neck cancer is the sixth most common cancer worldwide and laryngeal cancer represents the largest subgroup. However, the molecular mechanism underlying its malignant behavior and progression is not clarified. Accumulating evidence has shown that Notch1 signaling pathway plays a central role in carcinogenesis, but its potential role in regulating the development of laryngeal carcinoma, has not been characterized. Here, we identified that Notch1 signaling pathway was activated in laryngeal carcinoma accompanied with up-regulation of Notch1 and Hes1 expression. Overexpression of Notch1 in laryngeal carcinoma cell line Hep-2 led to suppression of tumor cellular proliferation and arrested cell cycle in the G(0)/G(1) phase and induced cell apoptosis, which were coupled with the down-regulation of cyclin D1, cyclin E, cdk2 and bcl-2 and up-regulation of caspase-3, caspase-9 and p53. Most importantly, up-regulation of Notch1 expression also reduced the migration of Hep-2 cells, which was closely associated with down-regulation of MMP-2 and MMP-9. The finding may lay a foundation for further investigations into the Notch1 signaling pathway as a potential target for laryngeal carcinoma.
引用
收藏
页码:815 / 823
页数:9
相关论文
共 29 条
[1]
Notch signaling: Cell fate control and signal integration in development [J].
Artavanis-Tsakonas, S ;
Rand, MD ;
Lake, RJ .
SCIENCE, 1999, 284 (5415) :770-776
[2]
ASSOCIATION OF MMP-2 ACTIVATION POTENTIAL WITH METASTATIC PROGRESSION IN HUMAN BREAST-CANCER CELL-LINES INDEPENDENT OF MMP-2 PRODUCTION [J].
AZZAM, HS ;
ARAND, G ;
LIPPMAN, ME ;
THOMPSON, EW .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (21) :1758-1764
[3]
Matrix metalloproteinases and tumor metastasis [J].
Deryugina, EI ;
Quigley, JP .
CANCER AND METASTASIS REVIEWS, 2006, 25 (01) :9-34
[4]
Cyclin E in human cancers [J].
Donnellan, R ;
Chetty, R .
FASEB JOURNAL, 1999, 13 (08) :773-780
[5]
Donnellan R, 1998, J CLIN PATHOL-MOL PA, V51, P1
[6]
Notch1 and Notch2 have opposite effects on embryonal brain tumor growth [J].
Fan, X ;
Mikolaenko, I ;
Elhassan, I ;
Ni, XZ ;
Wang, YY ;
Ball, D ;
Brat, DJ ;
Perry, A ;
Eberhart, CG .
CANCER RESEARCH, 2004, 64 (21) :7787-7793
[7]
The p53 pathway: positive and negative feedback loops [J].
Harris, SL ;
Levine, AJ .
ONCOGENE, 2005, 24 (17) :2899-2908
[8]
MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis [J].
Hiratsuka, S ;
Nakamura, K ;
Iwai, S ;
Murakami, M ;
Itoh, T ;
Kijima, H ;
Shipley, JM ;
Senior, RM ;
Shibuya, M .
CANCER CELL, 2002, 2 (04) :289-300
[9]
An activated mTOR/p70S6K signaling pathway in esophageal squamous cell carcinoma cell lines and inhibition of the pathway by rapamycin and siRNA against mTOR [J].
Hou, Guiqin ;
Xue, Lexun ;
Lu, Zhaoming ;
Fan, Tianli ;
Tian, Fang ;
Xue, Yanli .
CANCER LETTERS, 2007, 253 (02) :236-248
[10]
Husdal A, 2006, CELL ONCOL, V28, P107