GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by. Kao, S., Wang, W., Chen, C., Chang, Y., Wu, Y., Wang, Y., Wang, S., Nesvizhskii, A. I., Chen, Y., Hong, T., & Yang, P. Oncogene, 33(24):3172–3182, June, 2014.
doi  abstract   bibtex   
Glycogen synthase kinase 3 beta (GSK3beta) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3beta-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3beta-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3beta-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.
@article{kao_gsk3beta_2014,
	title = {{GSK}3beta controls epithelial-mesenchymal transition and tumor metastasis by},
	volume = {33},
	issn = {1476-5594 0950-9232},
	doi = {10.1038/onc.2013.279},
	abstract = {Glycogen synthase kinase 3 beta (GSK3beta) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3beta-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3beta-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not  degraded by CHIP. The accumulation of nondegradable Slug may further lead to the  repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3beta-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.},
	language = {eng},
	number = {24},
	journal = {Oncogene},
	author = {Kao, S.-H. and Wang, W.-L. and Chen, C.-Y. and Chang, Y.-L. and Wu, Y.-Y. and Wang, Y.-T. and Wang, S.-P. and Nesvizhskii, A. I. and Chen, Y.-J. and Hong, T.-M. and Yang, P.-C.},
	month = jun,
	year = {2014},
	pmid = {23851495},
	pmcid = {PMC4096338},
	keywords = {*Epithelial-Mesenchymal Transition, Animals, Blotting, Western, Cadherins/genetics/*metabolism, Carcinoma, Non-Small-Cell Lung/metabolism/*secondary, Cell Movement, Cell Proliferation, Cohort Studies, Gene Expression Regulation, Neoplastic, Glycogen Synthase Kinase 3 beta, Glycogen Synthase Kinase 3/genetics/*metabolism, Humans, Immunoenzyme Techniques, Immunoprecipitation, Lung Neoplasms/metabolism/*pathology, Mice, Mice, Inbred NOD, Mice, Nude, Phosphorylation, Proteolysis, Proteomics, RNA, Messenger/genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Snail Family Transcription Factors, Transcription Factors/genetics/*metabolism, Tumor Cells, Cultured, Ubiquitin-Protein Ligases/genetics/*metabolism, Ubiquitin/metabolism, Xenograft Model Antitumor Assays},
	pages = {3172--3182}
}

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