@article {206,
	title = {CUL4A induces epithelial-mesenchymal transition and promotes cancer metastasis by regulating ZEB1 expression.},
	journal = {Cancer Res},
	volume = {74},
	year = {2014},
	month = {2014 Jan 15},
	pages = {520-31},
	abstract = {<p>The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.</p>},
	keywords = {Animals, Breast, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, Cullin Proteins, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Histones, Homeodomain Proteins, Humans, Kruppel-Like Transcription Factors, Mammary Neoplasms, Experimental, Mice, Mice, Nude, Neoplasm Metastasis, Neoplasm Transplantation, Promoter Regions, Genetic, Signal Transduction, Transcription Factors},
	issn = {1538-7445},
	doi = {10.1158/0008-5472.CAN-13-2182},
	author = {Wang, Yunshan and Wen, Mingxin and Kwon, Yongwon and Xu, Yangyang and Liu, Yueyong and Zhang, Pengju and He, Xiuquan and Wang, Qin and Huang, Yurong and Jen, Kuang-Yu and LaBarge, Mark A and You, Liang and Kogan, Scott C and Gray, Joe W and Jiang-Hua Mao and Wei, Guangwei}
}
