Looking beyond the Wnt pathway for the deep nature of β‐catenin

Fagotto, François

doi:10.1038/embor.2013.45

Cited by 94 publications

(80 citation statements)

References 112 publications

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“…Further studies were conducted to examine whether NDRG1 could modulate the downstream effects of b-catenin. When expressed in the nucleus, b-catenin functions as part of a transcription factor complex to upregulate the transcription of proto-oncogenes, such as cyclin D1 (MacDonald et al, 2009;Clevers and Nusse, 2012;Fagotto, 2013). Therefore, the effect of NDRG1 overexpression and silencing on cyclin D1 expression was examined.…”

Section: Ndrg1 Inhibits B-catenin Phosphorylation At Ser33/37 and Thr41mentioning

confidence: 99%

The metastasis suppressor, NDRG1, modulates β-Catenin phosphorylation and nuclear translocation by mechanisms involving FRAT1 and PAK4

Jin¹,

Liu²,

Menezes³

et al. 2014

Journal of Cell Science

123

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N-myc downstream-regulated gene 1 (NDRG1) is a potent metastasis suppressor that has been demonstrated to inhibit the transforming growth factor b (TGF-b)-induced epithelial-tomesenchymal transition (EMT) by maintaining the cell-membrane localization of E-cadherin and b-catenin in prostate and colon cancer cells. However, the precise molecular mechanism remains unclear. In this investigation, we demonstrate that NDRG1 inhibits the phosphorylation of b-catenin at Ser33/37 and Thr41 and increases the levels of non-phosphorylated b-catenin at the plasma membrane in DU145 prostate cancer cells and HT29 colon cancer cells. The mechanism of inhibiting b-catenin phosphorylation involves the NDRG1-mediated upregulation of the GSK3b-binding protein FRAT1, which prevents the association of GSK3b with the Axin1-APC-CK1 destruction complex and the subsequent phosphorylation of b-catenin. Additionally, NDRG1 is shown to modulate the WNT-b-catenin pathway by inhibiting the nuclear translocation of b-catenin. This is mediated through an NDRG1-dependent reduction in the nuclear localization of p21-activated kinase 4 (PAK4), which is known to act as a transporter for b-catenin nuclear translocation. The current study is the first to elucidate a unique molecular mechanism involved in the NDRG1-dependent regulation of b-catenin phosphorylation and distribution.

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Section: Ndrg1 Inhibits B-catenin Phosphorylation At Ser33/37 and Thr41mentioning

confidence: 99%

The metastasis suppressor, NDRG1, modulates β-Catenin phosphorylation and nuclear translocation by mechanisms involving FRAT1 and PAK4

Jin¹,

Liu²,

Menezes³

et al. 2014

Journal of Cell Science

123

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“…Both CM1 and CM2 enhanced the expression of nuclear β-catenin, a key player in the regulation of follicle cell cycle, cell adhesion and signaling (Fagotto 2013), by HaCaT upon short-term treatment (24 hrs, Fig. 3C, Schemes 1-4).…”

Section: Expression Of Metabolic Markersmentioning

confidence: 99%

Dermal‐Epidermal Cross‐Talk: Differential Interactions With Microvascular Endothelial Cells

Bassino

Vallariello

Gasparri

et al. 2016

Journal Cellular Physiology

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The biological importance of circulatory blood supply and angiogenesis for hair growth is now well recognized, but the their regulatory mechanisms require more mechanistic investigation. In vitro cocultures and tricultures can be successfully employed to greatly improve our knowledge on paracrine crosstalk between cell types that populate the dermal-epidermal interface and cutaneous vasculature. Here we report that human dermal fibroblasts (NHDF) promote viability and proliferation of microvascular endothelial cells (HMVEC), while HMVEC are not mitogenic for NHDF. In triculture setup, conditioned media obtained by cocultures (HMVEC/NHDF or HMVEC/follicle fibroblasts) differently modulate growth and proliferation of keratinocytes and alter the expression of metabolic and pro-inflammatory markers. In conclusion, tricultures were successfully employed to characterize in vitro dermal-epithelial and endothelial interactions and could integrate ex vivo and in vivo approaches by the use of high-throughput and standardized protocols in controlled conditions. 3 INTRODUCTIONHuman cutaneous vasculature (CV) is organized in two major plexuses of blood vessels and capillaries can also be found within dermal papilla of hair follicle (HF) structures (Yano et al., 2001). In the adult, skin angiogenesis is still thought to be restricted to pathological conditions such as wound healing (Tonnesen et al., 2000), hyperproliferative inflammatory skin diseases like psoriasis (Varricchi et al., 2015), and in association with a wide range of tumors (Stapor et al., 2014). Physiological development and cycling of HF depends on the interaction between epithelial and mesenchymal cells (Schmidt-Ullrich et al., 2005), being able to develop and grow without a direct blood supply, as revealed by different organ culture techniques (Hardy et al., 1992;Philpott et al., 1999). However, blood supply is essential for long term hair maintenance, bringing nutrients, growth factors, cytokines and other bioactive molecules. In particular, vascular endothelial growth factor (VEGF), a key player in angiogenesis and vascular permeability, controls hair growth and follicle size (Yano et al., 2001). Conversely, in vitro and ex vivo evidences report that cytokines such as IL-1α are negative regulators of hair cycle (Hamada et al., 2003;Boivin et al., 2006;Harmon et al., 1993).The intensive circulatory support during anagen suggests its association with the high metabolic activity of HF matrix cells and insufficient blood supply can lead to HF diseases (Schmidt-Ullrich et al., 2005). Moreover, anagen HF, similarly to interfollicular epidermis, display angiogenic properties in vivo (Schmidt-Ullrich et al., 2005). Several techniques have been developed to characterize HF reconstitution and skin wound repair in more detail, both in vivo and in vitro.The hair inductive properties of dermal cells were first shown by Oliver et al., (1967) in which DP were transposed beneath the upper half of amputated vibrissa HF. Recently, two hair regeneration models were e...

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“…Wnt signaling is relevant in terms of one of its key downstream components, namely β-catenin. This protein is a signaling molecule and a component of focal adhesions, which forms a complex with E-cadherin and α-catenin (50). Therefore, miR-183 may be involved in the regulatory network of intercellular junctions ( Fig.…”

Section: Signalling Cascades With Microrna Interactionmentioning

confidence: 99%

Diverse microRNAs with convergent functions regulate tumorigenesis

2015

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Abstract. MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-β, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks. IntroductionMicroRNAs (miRNAs) are small non-coding RNAs of 21-25 nucleotides in length that control gene expression via post-transcriptional regulation (1). Contrasting with the maturation process of normal coding RNAs, the miRNA genes are initially transcribed by RNA polymerase II into a primary transcript in the nucleus, where the hairpin structure is processed into precursor miRNA by a microprocessing complex that includes Drosha and DiGeorge syndrome chromosomal (or critical) region 8 (DGCR8) (1). Subsequently, the ~70 nucleotide-long precursor miRNA is exported into the cytoplasm, where it undergoes secondary processing by Dicer, and one strand of the hairpin is then incorporated into a ribonucleoprotein complex known as miRNA-induced silencing complex (1). Once matured, a single miRNA may target miscellaneous messenger RNAs (mRNAs), and an individual mRNA may be regulated by various miRNAs (1). miRNAs have significant roles during stem cell maintenance and differentiation (2). In addition, they have frequently been used as markers for certain types of cancer cells, by comparing the measured levels of known miRNAs with those present in their wild-type counterparts (2,3). Screens investigating differential expression of miRNAs in various cancer cell populations have been previously performed. The present review will focus on the results of five screens conducted in the past recent years, which investigated prostate cancer (3), neuroblastoma (4), pancreatic cancer (5), chronic myeloid leukemia (CML) (6) and osteosarcoma cells (7). Specifically, Liu et al (3) used three prostate cancer metastatic cell lines, namely LAPC9, LAPC4 and Du145 [bone cluster of differentiation (CD)44 + /CD44 -subpopulation sorting based on LAPC9, LAPC4 and Du145 cell lines; side population (SP)/non-SP sorting based on LAPC9 cell line; and CD133 + /CD133 -subpopulation sorting based on LAPC4 cell line], and compared the expression levels of miscellaneous miRNAs (with vs. without markers) in these cells. Following testing for 324 DGCR8 miRNAs by reverse transcription-quantitative polymerase chain reaction, 137 miRNAs were identified to be expressed in the three ce...

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Looking beyond the Wnt pathway for the deep nature of β‐catenin

Cited by 94 publications

References 112 publications

The metastasis suppressor, NDRG1, modulates β-Catenin phosphorylation and nuclear translocation by mechanisms involving FRAT1 and PAK4

The metastasis suppressor, NDRG1, modulates β-Catenin phosphorylation and nuclear translocation by mechanisms involving FRAT1 and PAK4

Dermal‐Epidermal Cross‐Talk: Differential Interactions With Microvascular Endothelial Cells

Diverse microRNAs with convergent functions regulate tumorigenesis

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