Document Detail

Expression of Slug is regulated by c-Myb and is required for invasion and bone marrow homing of cancer cells of different origin.
MedLine Citation:
PMID:  20622260     Owner:  NLM     Status:  MEDLINE    
In metastatic cancer cells, the process of invasion is regulated by several transcription factors that induce changes required for migration and resistance to apoptosis. Slug (SNAI2, Snail2) is involved in epithelial mesenchymal transition in physiological and in pathological contexts. We show here that in embryonic kidney, colon carcinoma, chronic myeloid leukemia-blast crisis, and in neuroblastoma cells, expression of Slug is transcriptionally regulated by c-Myb via Myb binding sites in the 5'-flanking region and in the first intron of the slug gene. In embryonic kidney and neuroblastoma cells, c-Myb induced vimentin, fibronectin, and N-cadherin expression and membrane ruffling via actin polymerization consistent with the acquisition of a mesenchymal-like phenotype. Furthermore, down-regulation of endogenous c-Myb levels in colon carcinoma cells led to increased expression of E-cadherin and reduced levels of vimentin. Some of these changes are predominantly Slug-dependent as Slug silencing via RNA interference (RNAi) reverts the cells to a quasi-parental condition. Changes in gene expression and morphology induced by c-Myb-activated Slug correlated with increased ability to migrate (embryonic kidney) and to invade through a Matrigel membrane (embryonic kidney, colon carcinoma, neuroblastoma). c-Myb-dependent Slug expression was also essential for the homing of chronic myeloid leukemia K562 cells to the bone marrow. In summary, we show here that the proto-oncogene c-Myb controls Slug transcription in tumor cells of different origin. Such a regulatory pathway contributes to the acquisition of invasive properties that are important for the metastatic process.
Barbara Tanno; Fabiola Sesti; Vincenzo Cesi; Gianluca Bossi; Giovanna Ferrari-Amorotti; Rita Bussolari; Donatella Tirindelli; Bruno Calabretta; Giuseppe Raschellà
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-13     Completed Date:  2010-09-28     Revised Date:  2012-04-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29434-45     Citation Subset:  IM    
Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), Research Center Casaccia, Laboratory of Radiation Biology and Biomedicine, 00123 Rome, Italy.
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MeSH Terms
Apoptosis / drug effects,  genetics
Blotting, Western
Bone Marrow / pathology*
Cell Line
Cell Line, Tumor
Chromatin Immunoprecipitation
Etoposide / pharmacology
Flow Cytometry
Introns / genetics
Mice, SCID
Neoplasm Metastasis / genetics,  physiopathology
Polymerase Chain Reaction
Promoter Regions, Genetic / genetics
Protein Binding
Proto-Oncogene Proteins c-myb / genetics,  metabolism*
Transcription Factors / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/Proto-Oncogene Proteins c-myb; 0/Transcription Factors; 0/snail family transcription factors; 33419-42-0/Etoposide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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