Hypoxia triggers a Nur77-beta-catenin feed-forward loop to promote the invasive growth of colon cancer cells

CORC > 厦门大学 > 生命科学－已发表论文

	Hypoxia triggers a Nur77-beta-catenin feed-forward loop to promote the invasive growth of colon cancer cells
	To, S. K. Y. ; Zeng, W-J ; Zeng, J-Z ; Wong, A. S. T. ; Ceng JZ(曾锦章)
刊名	http://dx.doi.org/10.1038/bjc.2013.816
	2014-02-18
关键词	EPITHELIAL-MESENCHYMAL TRANSITION BETA-CATENIN COLORECTAL-CANCER C-JUN GENE-EXPRESSION KINASE PATHWAY ACTIVATION PROTEIN NUR77 TCF
英文摘要	Hong Kong Research Grant Council grant NSFC/RGC [30931160431/N_HKU 735/09]; Hong Kong Research Grant Council grant NSFC [31340029]; Croucher Senior Research Fellowship; Background: beta-Catenin is a potent oncogenic protein in colorectal cancer (CRC), but the targets and regulation of this important signalling molecule are not completely understood. Hypoxia is a prominent feature of solid tumours that contributes to cancer progression. Methods: Here, we analysed the regulation between Nur77 and beta-catenin under hypoxic conditions. Cell proliferation, migration, and invasion assays were performed to assess functional consequences. Results: We showed that hypoxia stimulated co-upregulation of beta-catenin and Nur77 in a number of human CRC cell lines. Interestingly, expression of beta-catenin and Nur77 by hypoxia formed a mutual feedback regulation circuits that conferred aggressive growth of CRC. Overexpression of beta-catenin increased Nur77 transcription through hypoxia-inducible factor-1 alpha rather than T-cell factor. Nur77-mediated activation of beta-catenin by hypoxia was independent of both DNA binding and transactivation. Further, we showed that hypoxic activation of beta-catenin was independent of the classical adenomatous polyposis coli and p53 pathways, but stimulated by phosphatidylinositol 3-kinase/Akt in a Nur77-dependent manner. Under hypoxic conditions, enhanced beta-catenin and Nur77 expression synergistically stimulated CRC cell migration, invasion, and epithelial-mesenchymal transition. Conclusion: These findings provide a novel molecular mechanism for hypoxic CRCs that may contribute to tumour progression, and its targeting may represent an effective therapeutic avenue.
语种	英语
出版者	NATURE PUBLISHING GROUP
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90828]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	To, S. K. Y.,Zeng, W-J,Zeng, J-Z,et al. Hypoxia triggers a Nur77-beta-catenin feed-forward loop to promote the invasive growth of colon cancer cells[J]. http://dx.doi.org/10.1038/bjc.2013.816,2014.
APA	To, S. K. Y.,Zeng, W-J,Zeng, J-Z,Wong, A. S. T.,&曾锦章.(2014).Hypoxia triggers a Nur77-beta-catenin feed-forward loop to promote the invasive growth of colon cancer cells.http://dx.doi.org/10.1038/bjc.2013.816.
MLA	To, S. K. Y.,et al."Hypoxia triggers a Nur77-beta-catenin feed-forward loop to promote the invasive growth of colon cancer cells".http://dx.doi.org/10.1038/bjc.2013.816 (2014).