NOTCH1信号通路在涎腺腺样囊性癌中促进细胞生长、抗凋亡和转移。
NOTCH1 signaling contributes to cell growth, anti-apoptosis and metastasis in salivary adenoid cystic carcinoma.
作者信息
Su Bo-Hua, Qu Jing, Song Min, Huang Xiao-Yu, Hu Xiao-Meng, Xie Jian, Zhao Yong, Ding Lin-Can, She Lin, Chen Jiang, Lin Li-Song, Lin Xu, Zheng Da-Li, Lu You-Guang
机构信息
Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China. These authors contributed equally to this work.
Department of Preventive Dentistry, Affiliated Stomatological Hospital, Fujian Medical University, Fuzhou, China.
出版信息
Oncotarget. 2014 Aug 30;5(16):6885-95. doi: 10.18632/oncotarget.2321.
BACKGROUND
Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC.
METHODS
We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR.
RESULTS
Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis.
CONCLUSIONS
The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.
背景
大量研究报道了Notch信号通路的肿瘤抑制和致癌作用，表明Notch活性以复杂的、依赖于背景的方式调节肿瘤生物学。本研究的目的是确定NOTCH1在涎腺腺样囊性癌（SACC）细胞生长和转移中的作用。
方法
我们使用免疫组织化学染色分析了NOTCH1在临床SACC样本中的表达。我们沉默NOTCH1的表达并过表达激活的NOTCH1，以阐明NOTCH1对增殖、迁移和侵袭的影响。通过实时PCR验证NOTCH1靶基因。
结果
我们的结果表明，与正常组织相比，SACC组织中NOTCH1上调，与无转移的SACC组织相比，有转移和复发的SACC组织中这种上调进一步增强。SACC细胞中NOTCH1的过表达促进细胞生长、迁移和侵袭，而NOTCH1的敲低通过诱导细胞凋亡抑制体外细胞增殖和体内致瘤性。
结论
本研究结果表明NOTCH1在SACC的细胞生长、抗凋亡和转移中起关键作用。因此，NOTCH1抑制剂可能通过抑制癌细胞生长和转移在治疗SACC患者方面具有潜在的治疗应用。
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