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Expression of slug is regulated by c-Myb and is required for invasion and bone marrow homing of cancer cells of different origin

TitoloExpression of slug is regulated by c-Myb and is required for invasion and bone marrow homing of cancer cells of different origin
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2010
AutoriTanno, Barbara, Sesti F., Cesi Vincenzo, Bossi G., Ferrari-Amorotti G., Bussolari R., Tirindelli D., Calabretta B., and Raschellà G.
RivistaJournal of Biological Chemistry
Volume285
Paginazione29434-29445
ISSN00219258
Parole chiaveActin polymerization, animal, animal cell, animal experiment, animal tissue, Animals, Apoptosis, article, Binding energy, binding site, Binding Sites, biochemistry, blast cell crisis, Blotting, Bone, bone marrow, cancer cell, Cancer cells, cancer invasion, cell death, cell homing, cell invasion, Cell Line, cell migration, cell strain HEK293, cell strain k 562, chromatin immunoprecipitation, Chronic myeloid leukemia, Chronic myeloid leukemias, Colon carcinoma, Colon carcinoma cells, controlled study, Different origins, Diseases, DNA flanking region, down regulation, Down-Regulation, drug effects, E-cadherins, Embryo, embryonic structures, Epithelial-Mesenchymal Transition, etoposide, fibronectin, Flanking regions, Flow cytometry, gene expression regulation, gene silencing, Genetic, genetics, human, human cell, human tissue, Humans, intron, Introns, K562 Cells, kidney, Laws and legislation, Matrigel, Membrane ruffling, metabolism, metastasis, Metastatic cancer cells, Mice, mouse, N-cadherin, Neoplasm Metastasis, nerve cell adhesion molecule, neuroblastoma cell, Neuroblastoma cells, Neuroblastomas, nonhuman, Pathology, pathophysiology, Polymerase Chain Reaction, priority journal, promoter region, Promoter Regions, protein analysis, protein binding, protein c Myb, protein expression, protein function, protein induction, proto oncogene, Proto-Oncogene Proteins c-myb, regulatory mechanism, Regulatory pathway, RNA, RNA Interference, SCID, SCID mouse, snail family transcription factors, Transcription, transcription factor, transcription factor Slug, Transcription Factors, transcription regulation, Tumor, tumor cell line, Tumor Cells, uvomorulin, vimentin, Western, Western blotting
Abstract

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. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-77956534980&doi=10.1074%2fjbc.M109.089045&partnerID=40&md5=57ecd7e9692c99fe6af2cb19e01d35bc
DOI10.1074/jbc.M109.089045
Citation KeyTanno201029434