CD44细胞
癌症研究
癌症
转移
生物
MAPK/ERK通路
激酶
细胞培养
癌细胞
体内
细胞
细胞生物学
生物化学
遗传学
生物技术
作者
Nancy P. Judd,Ashley E. Winkler,Oihana Murillo,Joshua J. Brotman,Jonathan H. Law,James S. Lewis,Gavin P. Dunn,Jack D. Bui,John B. Sunwoo,Ravindra Uppaluri
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2012-01-01
卷期号:72 (1): 365-374
被引量:170
标识
DOI:10.1158/0008-5472.can-11-1831
摘要
Carcinogen-induced oral cavity squamous cell carcinoma (OSCC) incurs significant morbidity and mortality and constitutes a global health challenge. To gain further insight into this disease, we generated cell line models from 7,12-dimethylbenz(a)anthracene-induced murine primary OSCC capable of tumor formation upon transplantation into immunocompetent wild-type mice. Whereas several cell lines grew rapidly and were capable of metastasis, some grew slowly and did not metastasize. Aggressively growing cell lines displayed ERK1/2 activation, which stimulated expression of CD44, a marker associated with epithelial to mesenchymal transition and putative cancer stem cells. MEK (MAP/ERK kinase) inhibition upstream of ERK1/2 decreased CD44 expression and promoter activity and reduced cell migration and invasion. Conversely, MEK1 activation enhanced CD44 expression and promoter activity, whereas CD44 attenuation reduced in vitro migration and in vivo tumor formation. Extending these findings to freshly resected human OSCC, we confirmed a strict relationship between ERK1/2 phosphorylation and CD44 expression. In summary, our findings identify CD44 as a critical target of ERK1/2 in promoting tumor aggressiveness and offer a preclinical proof-of-concept to target this pathway as a strategy to treat head and neck cancer.
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