Notch signaling induces EMT in OSCC cell lines in a hypoxic environment.
Notch signaling induces EMT in OSCC cell lines in a hypoxic environment.
复制标题
DOI：
10.3892/ol.2013.1549
复制
发表时间：
2013-11
期刊：
影响因子：
2.9
通讯作者：
Nakamura N
中科院分区：
文献类型：
--
作者：
Ishida T;Hijioka H;Kume K;Miyawaki A;Nakamura N
上皮-间质转化（EMT）是恶性肿瘤获得侵袭性的早期步骤。已经阐明，肿瘤微环境影响许多不同癌的恶性程度，特别是，低氧环境诱导EMT。Notch信号的激活诱导EMT，但尚不清楚Notch通路如何参与缺氧条件下的口腔鳞状细胞癌（OSCC）。在低氧（1%O2）和常氧（21%O2）条件下培养三种OSCC细胞系进行检测。免疫组化法检测E-cadherin的表达。分别通过伤口愈合和侵袭试验检查细胞运动性和侵袭性。通过qPCR分析Notch途径分子的表达。缺氧增加Notch受体、配体和靶基因以及Snail的mRNA表达。缺氧可降低E-cadherin的表达，增强OSCC细胞的运动性和侵袭性。Notch特异性抑制剂γ-分泌酶抑制剂（γ-secretase inhibitor，γ-secretase inhibitor，γ-secretase inhibitor）可阻断缺氧引起的上述效应。这些结果表明，缺氧诱导EMT在OSCC细胞系通过激活Notch信号，和Notch信号通路的抑制，抑制EMT可能是一个有用的方法，用于治疗OSCC。
Epithelial-mesenchymal transition (EMT) is an early step in the acquisition of invasiveness by malignant tumors. It has been clarified that the tumor microenvironment affects malignancy in a number of different carcinomas, in particular, that a hypoxic environment induces EMT. Activation of Notch signaling induces EMT, but it remains unclear how the Notch pathway is involved in oral squamous cell carcinoma (OSCC) under hypoxia. Three OSCC cell lines were cultured for examination under hypoxic (1% O2) and normoxic (21% O2) conditions. Expression of E-cadherin was investigated as a hallmark of EMT by immunohistochemical examination. Cell motility and invasion were examined by wound-healing and invasion assays, respectively. The expression of Notch pathway molecules was analyzed by qPCR. Hypoxia increased the mRNA expression of Notch receptors, ligands and target genes, and Snail. Hypoxia decreased the expression of E-cadherin, and increased the motility and invasiveness of OSCC cell lines. γ-secretase inhibitor, a Notch-specific inhibitor, prevented these effects caused by h-ypoxia. These findings suggest that hypoxia induces EMT in OSCC cell lines via activation of Notch signaling, and inhibition of the Notch signaling pathway to suppress EMT may be a useful approach for the treatment of OSCC.
登录
查看更多内容
影响因子：
3.5
作者：
Hill, Richard P.;Marie-Egyptienne, Delphine T.;Hedley, David W.
通讯作者：
Hedley, David W.
影响因子：
50.3
作者：
Ansieau, Stephane;Bastid, Jeremy;Puisieux, Alain
通讯作者：
Puisieux, Alain
影响因子：
50.3
作者：
Moody, SE;Perez, D;Chodosh, LA
通讯作者：
Chodosh, LA
影响因子：
3.7
作者：
Lin, Jen-Tsun;Chen, Mu-Kuan;Chang, Pey-Jium
通讯作者：
Chang, Pey-Jium
影响因子：
5.2
作者：
Pietras, Alexander;von Stedingk, Kristoffer;Axelson, Hakan
通讯作者：
Axelson, Hakan