Reversible SUMOylation of TBL1-TBLR1 Regulates β-Catenin-Mediated Wnt Signaling

Choi, Hyo‐Kyoung; Choi, Kyung‐Chul; Yoo, Jeong-Eun; Song, Minju; Ko, Suk Jin; Kim, Chul Hoon; Ahn, Jin-Hyun; Chun, Kyung–Hee; Yook, Jong In; Yoon, Ho‐Geun

doi:10.1016/j.molcel.2011.05.027

Cited by 96 publications

(92 citation statements)

References 35 publications

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“…Combining our results with those of previous studies of the biological function and mechanism of TBLR1 (An et al , 2003; Perissi et al , 2004; Li and Wang, 2008; Choi et al , 2011), we decided to test whether the Snail and Twist protein levels were influenced in the stable Hela and Siha cell lines. Western blotting showed that the expressions of Snail and Twist were significantly higher in TBLR1-overexpressing tumours and lower in TBLR1-silenced tumours than the respective control tumours (Figures 3A and 6A).…”

Section: Resultsmentioning

confidence: 70%

“…In addition, Hela cells have been used as materials to show that histone deacetylase 3 includes TBLR1 localises to the mitotic spindle and is required for kinetochore–microtubule attachment (Ishii et al , 2008). Moreover, TBLR1 expression was upregulated in human primary lung squamous cell carcinoma, breast cancer and colon cancer cells, suggesting that TBLR1 is involved in promoting tumour progression or blocking apoptosis (Hoberg et al , 2004; Perissi et al , 2008; Choi et al , 2011). However, there has been no report on the expression of TBLR1 is correlated with clinical staging or cancer patient survival as a potential oncogene.…”

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confidence: 99%

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TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

Wang

Guo

et al. 2014

Br J Cancer

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Background:Invasion and metastasis remain a critical issue in cervical cancer. However, the underlying mechanism of it in cervical cancer remains unclear. The newly discovered protein, TBLR1, plays a crucial role in regulating various key cellular functions.Methods:In this study, western blot, real-time RT–PCR, immunohistochemical staining, 3D morphogenesis Matrigel culture, wound healing and Boyden chamber invasion assays, xenografted tumour model, luciferase assays, and chromatin immunoprecipitation assays were used.Results:The expression of TBLR1 in cervical cancer cell lines and tissues was significantly upregulated at both the RNA and protein levels compared with that in normal cervical cells. Statistical analysis suggested that TBLR1 as an independent prognostic factor was significantly correlated with the clinical stage, survival time and recurrence. Moreover, overexpression of TBLR1 in Hela and Siha cell lines promoted invasion in vitro and in vivo with the increases of the mesenchymal factors vimentin and fibronectin and decreases of the epithelial marker α-catenin. In contrast, RNAi-mediated knockdown of TBLR1 inhibited epithelial–mesenchymal transition in vitro and in vivo. Further study indicated that this might be mediated via the NF-κB and Wnt/β-Catenin signalling pathway, and involve regulation of Snail and Twist.Conclusions:The TBLR1 protein may be a prognostic marker in cervical cancer and play an important role in the invasion and metastasis of human cervical cancer.

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Section: Resultsmentioning

confidence: 70%

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confidence: 99%

TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

Wang

Guo

et al. 2014

Br J Cancer

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“…We found increased expression of the ER markers Bip and CHOP in As-Prdx6-transfected HT22 cells (Fig. 7D) (16,18,102), suggesting that reduced expression of Prdx6 initiated ER stress in HT22 cells. Furthermore, our experiments revealed that cells treated with hypoxia displayed higher expression of ER stress and/or apoptosis markers (Figs.…”

Section: Discussionmentioning

confidence: 85%

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

Chhunchha

Fatma

Kubo

et al. 2013

American Journal of Physiology-Cell Physiology

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Oxidative stress and endoplasmic reticulum (ER) stress are emerging as crucial events in the etiopathology of many neurodegenerative diseases. While the neuroprotective contributions of the dietary compound curcumin has been recognized, the molecular mechanisms underlying curcumin's neuroprotection under oxidative and ER stresses remains elusive. Herein, we show that curcumin protects HT22 from oxidative and ER stresses evoked by the hypoxia (1% O(2) or CoCl(2) treatment) by enhancing peroxiredoxin 6 (Prdx6) expression. Cells exposed to CoCl(2) displayed reduced expression of Prdx6 with higher reactive oxygen species (ROS) expression and activation of NF-κB with IκB phosphorylation. When NF-κB activity was blocked by using SN50, an inhibitor of NF-κB, or cells treated with curcumin, the repression of Prdx6 expression was restored, suggesting the involvement of NF-κB in modulating Prdx6 expression. These cells were enriched with an accumulation of ER stress proteins, C/EBP homologous protein (CHOP), GRP/78, and calreticulin, and had activated states of caspases 12, 9, and 3. Reinforced expression of Prdx6 in HT22 cells by curcumin reestablished survival signaling by reducing propagation of ROS and blunting ER stress signaling. Intriguingly, knockdown of Prdx6 by antisense revealed that loss of Prdx6 contributed to cell death by sustaining enhanced levels of ER stress-responsive proapoptotic proteins, which was due to elevated ROS production, suggesting that Prdx6 deficiency is a cause of initiation of ROS-mediated ER stress-induced apoptosis. We propose that using curcumin to reinforce the naturally occurring Prdx6 expression and attenuate ROS-based ER stress and NF-κB-mediated aberrant signaling improves cell survival and may provide an avenue to treat and/or postpone diseases associated with ROS or ER stress.

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“…In other words, TBL1XR1 can promote the transcription processes mediated by transcription factors, including NF-κB, nuclear receptors (NRs), Wnt/β-catenin and Notch pathways (Hoberg et al 2004;Choi et al 2011). Moreover, the functions of TBL1XR1 were distinct in different tumors.…”

Section: Introductionmentioning

confidence: 99%

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

2017

Tohoku J. Exp. Med.

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Transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) is a core component of the NCoR/SMRT transcription co-repressor complex, and its role in regulating cancer progression has been reported. Serous epithelial ovarian cancer (EOC) is the most common histological type of EOC. Here we explored the significance of TBL1XR1 expression in predicting outcomes of patients with serous EOC. Real-time quantitative PCR analysis showed that the expression level of TBL1XR1 mRNA was significantly higher in EOC tissues compared with adjacent non-tumorous tissues. The protein levels of TBL1XR1 in EOC tissues were assessed by immunohistochemistry, and the patients were classified into low-expression group (n = 62) and high-expression group (n = 54) according to the immunoreactivity. Prognostic significance of TBL1XR1 was evaluated by univariate and multivariate analyses, showing that over-expression of TBL1XR1 was correlated with poor prognosis. In addition, TBL1XR1 was positively associated with the lymph node metastasis of EOC. Because vascular endothelial growth factor (VEGF)-C is known as a critical mediator of lymph node metastasis, we measured the expression level of VEGF-C mRNA in EOC tissues and thus identified a positive correlation between TBL1XR1 and VEGF-C mRNA levels. Subsequently, using human EOC cell lines, we showed that silencing of TBL1XR1 decreased VEGF-C expression, suggesting that TBL1XR1 may function as an upstream regulator of VEGF-C in EOC. Furthermore, the proliferation and invasion of EOC cells were inhibited by TBL1XR1 silencing. In conclusion, TBL1XR1 overexpression may be an unfavorable prognostic factor for EOC. We also suggest that the TBL1XR1-VEGF-C axis may determine the EOC progression.

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Reversible SUMOylation of TBL1-TBLR1 Regulates β-Catenin-Mediated Wnt Signaling

Cited by 96 publications

References 35 publications

TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

TBLR1 is a novel prognostic marker and promotes epithelial–mesenchymal transition in cervical cancer

Curcumin abates hypoxia-induced oxidative stress based-ER stress-mediated cell death in mouse hippocampal cells (HT22) by controlling Prdx6 and NF-κB regulation

Over-Expression of TBL1XR1 Indicates Poor Prognosis of Serous Epithelial Ovarian Cancer

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