Expression of Slug Is Regulated by c-Myb and Is Required for Invasion and Bone Marrow Homing of Cancer Cells of Different Origin

Tanno, Barbara; Sesti, Fabiola; Cesi, Vincenzo; Bossi, Gianluca; Ferrari-Amorotti, Giovanna; Bussolari, Rita; Tirindelli, Donatella; Calabretta, Bruno; Raschellà, Giuseppe

doi:10.1074/jbc.m109.089045

Cited by 53 publications

(56 citation statements)

References 37 publications

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“…Interestingly, induction of Slug has been shown to be requisite in multiple model systems of metastatic progression for homing and colonization to distant metastatic sites (40). Data herein are concordant with such conclusions and validate the role of Slug in the progression to metastatic PCa.…”

Section: Figuresupporting

confidence: 78%

“…Interestingly, coexpression with cyclin D1b enhanced colony formation (∼10%) over that of Slug alone, indicating that while Slug expression is sufficient to drive cyclin D1b-mediated phenotypes, cyclin D1b regulates additional networks that promote anchorage independent growth. Previous studies in other model systems suggested that the ability of Slug to directly suppress CDH1 (encoding E-cadherin) underlies the prometastatic phenotypes associated with Slug expression (39,40). Surprisingly, induction of Slug was not sufficient to diminish extracellular levels of E-cadherin in this system ( Figure 5D).…”

Section: Figurementioning

confidence: 72%

See 1 more Smart Citation

Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes

Augello¹,

Burd²,

Birbe³

et al. 2012

J. Clin. Invest.

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Cyclin D1b is a splice variant of the cell cycle regulator cyclin D1 and is known to harbor divergent and highly oncogenic functions in human cancer. While cyclin D1b is induced during disease progression in many cancer types, the mechanisms underlying cyclin D1b function remain poorly understood. Herein, cell and human tumor xenograft models of prostate cancer were utilized to resolve the downstream pathways that are required for the protumorigenic functions of cyclin D1b. Specifically, cyclin D1b was found to modulate the expression of a large transcriptional network that cooperates with androgen receptor (AR) signaling to enhance tumor cell growth and invasive potential. Notably, cyclin D1b promoted AR-dependent activation of genes associated with metastatic phenotypes. Further exploration determined that transcriptional induction of SNAI2 (Slug) was essential for cyclin D1b-mediated proliferative and invasive properties, implicating Slug as a critical driver of disease progression. Importantly, cyclin D1b expression highly correlated with that of Slug in clinical samples of advanced disease. In vivo analyses provided strong evidence that Slug enhances both tumor growth and metastatic phenotypes. Collectively, these findings reveal the underpinning mechanisms behind the protumorigenic functions of cyclin D1b and demonstrate that the convergence of the cyclin D1b/AR and Slug pathways results in the activation of processes critical for the promotion of lethal tumor phenotypes.

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Section: Figuresupporting

confidence: 78%

Section: Figurementioning

confidence: 72%

Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes

Augello¹,

Burd²,

Birbe³

et al. 2012

J. Clin. Invest.

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“…Tanno et al (33) demonstrated that the expression of neuronal cadherin was increased in c-Myb-expressing HEK-293 and LAN-5 cells, and may be responsible for the biological function of c-Myb. In the present study, bioinformatic prediction and experimental data indicated that miR-548c-3p is able to target c-Myb.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-548c-3p inhibits T98G glioma cell proliferation and migration by downregulating c-Myb

Zhang

Xiao

et al. 2017

Oncology Letters

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Abstract. MicroRNAs (miRNAs/miRs) are short non-coding RNAs (between 20 and 22 nucleotides) that regulate gene expression by binding to the 3'-untranslated region of target mRNA, and preventing protein translation or inducing mRNA destabilization. miRNAs are predicted to target ~60% of all mRNAs, therefore providing a marked degree of regulation of a number of cellular processes. In the present study, the expression of miR-548c-3p was determined by reverse transcription-quantitative polymerase chain reaction analysis and demonstrated to be markedly downregulated in clinical malignant glioma tissues and the glioma T98G cell line compared with normal human brain tissue. Transfection of miR-548c-3p inhibited cell proliferation by inducing G 1 cell cycle arrest and also inhibited the migration of the T98G cells in vitro. Furthermore, a bioinformatic algorithm and a luciferase reporter assay identified proto-oncogene c-Myb (c-Myb) as a potential direct target of miR-548c-3p. Further experiments demonstrated that the inhibition of c-Myb by miR-548c-3p partially mediated the antitumor effect of miR-548c-3p. The results of the present study provide the novel insight that miR-548c-3p inhibits glioma tumorigenesis by targeting c-Myb. Therefore, miR-548c-3p may contribute to the development of improved glioma treatment.

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“…However, no direct interaction or regulatory elements were originally reported. More recently, a non-NC study using embryonic kidney, colon carcinoma, neuroblastomas and leukemia-blast cells identified a regulatory element recognized by cMyb controlling the expression of Snail2 and evocating an epithelial to mesenchymal transformation (Tanno et al, 2010). Collectively, these studies support an important role for cMyb within the NC-GRN.…”

Section: The Regulatory Elements Of Pax7 In Mammalsmentioning

confidence: 61%

Pax7 is regulated by cMyb during early neural crest development through a novel enhancer

et al. 2013

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SUMMARYThe neural crest (NC) is a migratory population of cells unique to vertebrates that generates many diverse derivatives. NC cells arise during gastrulation at the neural plate border (NPB), which is later elevated as the neural folds (NFs) form and fuse in the dorsal region of the closed neural tube, from where NC cells emigrate. In chick embryos, Pax7 is an early marker, and necessary component of NC development. Unlike other early NPB markers, which are co-expressed in lateral ectoderm, medial neural plate or posterior-lateral mesoderm, Pax7 early expression seems more restricted to the NPB. However, the molecular mechanisms controlling early Pax7 expression remain poorly understood. Here, we identify a novel enhancer of Pax7 in avian embryos that replicates the expression of Pax7 associated with early NC development. Expression from this enhancer is found in early NPB, NFs and early emigrating NC, but unlike Pax7, which is also expressed in mesodermal derivatives, this enhancer is not active in somites. Further analysis demonstrates that cMyb is able to interact with this enhancer and modulates reporter and endogenous early Pax7 expression; thus, cMyb is identified as a novel regulator of Pax7 in early NC development. KEY WORDS: Neural plate border, Neural crest, PAX7, cMyb, Enhancer, ChickPax7 is regulated by cMyb during early neural crest development through a novel enhancerStephanie Vadasz, Jonathan Marquez, Maria Tulloch, Natalia A. Shylo and Martín I. García-Castro* DEVELOPMENT 3692 regulatory elements and TFs that initiate the expression of Pax7 at the NPB have not been reported.Here, we identify a novel Pax7 cis-regulatory element that directs expression in the avian NPB, NFs and early migrating NC cells, similar to the endogenous Pax7 expression associated with early NC. This element does not provide expression in later NC or in mesoderm, where endogenous Pax7 is seen. Through mutagenesis and overexpression studies, we unveil cMyb as a regulator of this enhancer and of endogenous early Pax7 expression. Our study is the first to demonstrate the ability of cMyb to regulate a border specifier directly during NC development and thus proposes a fundamental role for cMyb during the early phases of the NC-GRN. MATERIALS AND METHODS Sequence conservation and TF-binding analysisSequence conservation was determined using VISTA Browser (Visel et al., 2007), over a 50 bp window with 70% conserved identity. Putative TFbinding sites were identified using the JASPAR core vertebrate database (Bryne et al., 2008). Plasmid constructsEnhancer constructs were PCR amplified (DNeasy Kit, Qiagen) from genomic chick or human DNA (a gift from J. Noonan, New Haven, CT, USA), and cloned into ptkEGFP (a gift from H. Kondoh, Osaka, Japan) or ptkmCherry (a gift from D. Meulemans, Boulder, CO, USA) using KpnI and XhoI. pRFP was generated by removing the miRNA cassette from pRFPRNAi (ARK Genomics). Deletion constructs were generated by first amplifying each end with primers containing 15 bp of internal overlapping sequence fol...

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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

Cited by 53 publications

References 37 publications

Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes

Convergence of oncogenic and hormone receptor pathways promotes metastatic phenotypes

MicroRNA-548c-3p inhibits T98G glioma cell proliferation and migration by downregulating c-Myb

Pax7 is regulated by cMyb during early neural crest development through a novel enhancer

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