Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation of class IIa HDACs

Ishikawa, Fumihiro; Miyoshi, Hiroyuki; Nose, Kiyoshi; Shibanuma, Motoko

doi:10.1038/onc.2009.387

Cited by 43 publications

(40 citation statements)

References 45 publications

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“…By contrast, in recurrent ER-positive mammary cancers, expression of MEF2s correlates with NOTCH1 protein levels (Pallavi et al, 2012). Although some reports point to a contribution of MEF2-dependent transcription to mammary gland neoplastic pathogenesis, data on the role of the MEF2-HDAC axis during normal gland development and homeostasis are lacking, and only little information is available on the role of the axis in epithelial cells (Ishikawa et al, 2010). Based on this evidence, we hypothesized that the MEF2-HDAC axis plays a role in the regulation of breast epithelial cell proliferation and/or differentiation.…”

Section: Introductionmentioning

confidence: 96%

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

Clocchiatti

Giorgio

Viviani

et al. 2015

Journal of Cell Science

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The myocyte enhancer factor 2 and histone deacetylase (MEF2-HDAC) axis is a master regulator of different developmental programs and adaptive responses in adults. In this paper, we have investigated the contribution of the axis to the regulation of epithelial morphogenesis, using 3D organotypic cultures of MCF10A cells as a model. We have demonstrated that MEF2 transcriptional activity is upregulated during acini formation, which coincides with exit from the proliferative phase. Upregulation of the transcription of MEF2 proteins is coupled to downregulation of HDAC7, which occurs independently from changes in mRNA levels, and proteasome-or autophagymediated degradation. During acini formation, the MEF2-HDAC axis contributes to the promotion of cell cycle exit, through the engagement of the CDK inhibitor CDKN1A. Only in proliferating cells can HDAC7 bind to the first intron of the CDKN1A gene, a region characterized by epigenetic markers of active promoters and enhancers. In cells transformed by the oncogene HER2 (ERBB2), acini morphogenesis is altered, MEF2 transcription is repressed and HDAC7 is continuously expressed. Importantly, reactivation of MEF2 transcriptional activity in these cells, through the use of a HER2 inhibitor or by enhancing MEF2 function, corrected the proliferative defect and re-established normal acini morphogenesis.

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Section: Introductionmentioning

confidence: 96%

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

Clocchiatti

Giorgio

Viviani

et al. 2015

Journal of Cell Science

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“…3,4 The large range of differentiative/adaptive responses, under class IIa HDACs supervision, finds confirmation in the assorted genetic programs such as: cell motility, interaction with the ECM, cell cycle and survival/apoptosis, monitored by these enzymes. [5][6][7][8] In particular, recent studies have underlined the intricate relationships between class IIa HDACs and metabolism. 9,10,11 Kinases such as AMPK and SIKs, which fine-tune metabolic adaptations can also modulate class IIa nuclear/cytoplasmic shuttling via phosphorylation of 14-3-3 binding sites.…”

Section: Introductionmentioning

confidence: 99%

Transformation by different oncogenes relies on specific metabolic adaptations

et al. 2016

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Metabolic adaptations are emerging as common traits of cancer cells and tumor progression. In vitro transformation of NIH 3T3 cells allows the analysis of the metabolic changes triggered by a single oncogene. In this work, we have compared the metabolic changes induced by H-RAS and by the nuclear resident mutant of histone deacetylase 4 (HDAC4). RAS-transformed cells exhibit a dominant aerobic glycolytic phenotype characterized by up-regulation of glycolytic enzymes, reduced oxygen consumption and a defect in complex I activity. In this model of transformation, glycolysis is strictly required for sustaining the ATP levels and the robust cellular proliferation. By contrast, in HDAC4/TM transformed cells, glycolysis is only modestly up-regulated, lactate secretion is not augmented and, instead, mitochondrial oxygen consumption is increased. Our results demonstrate that cellular transformation can be accomplished through different metabolic adaptations and HDAC4/TM cells can represent a useful model to investigate oncogene-driven metabolic changes besides the Warburg effect.

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“…In addition, Kumawat et al (36) reported that TGF-b1 induced the expression of Wnt-5a, but not Wnt-5b, in airway smooth muscle cells. There are also a few reports that demonstrate the upregulation of MMP-10 expression during TGF-b1-induced EMT (43,44). TGF-b1 plus EGF stimulation induces expression of MMP-10 and MMP-1 in HaCaT II-4 keratinocytes and promotes the invasion ability of cells growing on collagen type I gels (43), presumably through enhanced collagen degradation.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor-β1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis

et al. 2016

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Transcriptional induction of MMP-10 by TGF-β, mediated by activation of MEF2A and downregulation of class IIa HDACs

Cited by 43 publications

References 45 publications

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

The MEF2–HDAC axis controls proliferation of mammary epithelial cells and acini formation in vitro

Transformation by different oncogenes relies on specific metabolic adaptations

Transforming growth factor-β1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis

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