Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Ml, Nairismägi; Vislovukh, A. A.; Meng, Qingwei; Kratassiouk, Gueorgui; Beldiman, Cornelia; Petretich, Massimo; Groisman, Regina; Em, Füchtbauer; Harel‐Bellan, Annick; Groisman, Irina

doi:10.1038/onc.2011.650

Cited by 69 publications

(72 citation statements)

References 25 publications

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“…In response to stress, CPEB2 dissociates from the target transcript and allows the polyadenylate tail to elongate and/or alternative polyadenylation sites to be used followed by subsequent translation of the mRNA by the ribosomal complex (29 -33). Two such mRNA transcripts reported to be regulated by CPEB2 are HIF1␣ and TWIST1 (25)(26)(27)(28), factors strongly associated with cancer progression and the EMT. As we show that CPEB2A sensitizes TNBC cells to anoikis, one can hypothesize that CPEB2A is the specific isoform of CPEB2 acting as an inhibitor of HIF1␣ and TWIST1 polyadenylation and translation, As we also observed a previously unknown antagonism between the two CPEB2 splice variants, CPEB2A and -B, we can further hypothesize that CPEB2B has the opposing function.…”

Section: Discussionmentioning

confidence: 99%

“…The identity of the CPEB2 isoforms was confirmed by gel extraction of the PCR fragments followed by DNA sequencing, which verified that CPEB2A excludes 90 nucleotides corresponding to exon 4 of the CPEB2B gene (nucleic acids 1944 -2034; data not shown and Refs. [25][26][27][28]. The CPEB2B isoform is a recently discovered one that was partially characterized in murine models earlier this year (25)(26)(27)(28).…”

Section: Anoikis Resistance Enhances the Transformative Potential Ofmentioning

confidence: 99%

“…[25][26][27][28]. The CPEB2B isoform is a recently discovered one that was partially characterized in murine models earlier this year (25)(26)(27)(28). These data demonstrate that aberrantly spliced CPEB2 pre-mRNA produces the splice variant of CPEB2, CPEB2B, which is strongly associated with AnR in TNBC.…”

Section: Anoikis Resistance Enhances the Transformative Potential Ofmentioning

confidence: 99%

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The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer

Johnson

Griffin

et al. 2015

Journal of Biological Chemistry

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Background:The acquisition of anoikis resistance (AnR) is an important mechanism in metastasis. Results: AnR requires the up-regulation of the B isoform of CPEB2 via alternative RNA splicing (AS). Conclusion: CPEB2 AS is a key mechanism in both AnR and the metastasis of breast cancer (BC). Significance: Understanding the regulation of CPEB2 AS may lead to new targets for treatment of metastatic BC.

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Section: Discussionmentioning

confidence: 99%

Section: Anoikis Resistance Enhances the Transformative Potential Ofmentioning

confidence: 99%

Section: Anoikis Resistance Enhances the Transformative Potential Ofmentioning

confidence: 99%

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The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer

Johnson

Griffin

et al. 2015

Journal of Biological Chemistry

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“…Twist, a transcription factor, plays an important role in EMT and metastasis (35). CPEB1 interacts with Twist1 mRNA and down-regulates its expression; in the absence of CPEB1, Twist1 mRNA translation is elevated, which leads to EMT and metastasis (5,36). In addition, upon CPEB1 reduction, matrix metalloproteinase 9 (MMP-9) mRNA, which encodes a metastasis-promoting factor, undergoes poly(A) lengthening and enhanced translation (33).…”

Section: Cpeb1mentioning

confidence: 99%

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Chen

Tsai

Tseng

2016

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Abstract. Regulated mRNA translation plays an important role in normal cellular functions and cytoplasmic polyadenylation element binding proteins (CPEBs) are the key factors that control the elongation of poly(A) tail during translation. The expression of various Translation and Cytoplasmic Polyadenylation Element Binding Proteins (CPEBs)Regulated mRNA translation plays an important role in normal cellular functions (1, 2). The translation of an mRNA is divided into three steps: initiation, elongation and termination (1). Among them, translation initiation is the rate-limiting, the most complex and the main target for translational control mechanisms (3). The 5'end of all transcribed mRNAs contains a 5'cap and the other end is blocked by a long stretch, usually in the order of 200-500 nucleotides of adenine residues (poly(A) tail) (1). Both the cap and the poly(A) tail of mRNAs act synergistically to facilitate translation (1). The translation is affected by a number of factors that stimulate or inhibit the translation of specific mRNAs (1, 2). Among these factors, RNAbinding proteins that recognize specific motifs in the 3' untranslated region (3'UTR) of their targets, are important (1, 2, 4). Of these RNA-binding proteins, cytoplasmic polyadenylation element binding protein (CPEB) family are sequence-specific RNA-binding proteins and the key factors controling the elongation of the poly(A) tail and polyadenylation-induced translation (2,5,6). CPEB binds the cytoplasmic polyadenylation element (CPE) in the 3' untranslated regions of responding mRNAs (2, 7-9). CPEB-mediated effects on translation require at least two CPEs separated by less than 50 nucleotides in the target mRNA, which indicates the formation of CPEB-dimer (10). CPEBs can recruit the translational repression or cytoplasmic polyadenylation machineries to their target mRNAs and nucleate a complex of factors that regulates poly(A) elongation through a deadenylating enzyme (1,4,7,(11)(12)(13). 5673

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“…Of interest, Twist1 was described to be a master regulator of EMT in several breast epithelial cells including MCF10A. [28][29][30] …”

Section: Differential Gene Expression Analysismentioning

confidence: 99%

Twist1 and Slug mediate H2AX-regulated epithelial-mesenchymal transition in breast cells

et al. 2016

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The epithelial-mesenchymal transition (EMT) is thought to be essential for cancer metastasis. While chromatin remodeling is involved in EMT, which processes contribute to this remodeling remain poorly investigated. Recently, we showed that silencing or removal of the histone variant H2A.X induced mesenchymal-like characteristics, including activation of the EMT transcription factors, Slug and Zeb1 in human colon cancer cells. Here, we provide the evidence that H2A.X loss in human non-tumorigenic breast cell line MCF10A results in a robust EMT activation, as substantiated by a genome-wide expression analysis. Cells deficient for H2A.X exhibit enhanced migration and invasion, along with an activation of a set of mesenchymal genes and a concomitant repression of epithelial genes. In the breast model, the EMT-related transcription factor Twist1 cooperates with Slug to regulate EMT upon H2A.X Loss. Of interest, H2A.X expression level tightly correlates with Twist1, and to a lesser extent with Slug in the panel of human breast cancer cell lines of the NCI-60 datasets. These new findings indicate that H2A.X is involved in the EMT processes in cells of different origins but pairing with transcription factors for EMT may be tissue specific.

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Translational control of TWIST1 expression in MCF-10A cell lines recapitulating breast cancer progression

Cited by 69 publications

References 25 publications

The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer

The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2 Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer

Regulation of the Expression of Cytoplasmic Polyadenylation Element Binding Proteins for the Treatment of Cancer

Twist1 and Slug mediate H2AX-regulated epithelial-mesenchymal transition in breast cells

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