共查询到20条相似文献,搜索用时 546 毫秒
1.
Xiu‐lan Zhao Tao Sun Na Che Dan Sun Nan Zhao Xue‐yi Dong Qiang Gu Zhi Yao Bao‐cun Sun 《Journal of cellular and molecular medicine》2011,15(3):691-700
E‐cadherin loss is a key biological mechanism in tumour invasion. As a main regulator of epithelial‐mesenchymal transition (EMT) mechanism‐mediated invasion and metastasis, Twist1 plays an important role through its regulation of E‐cadherin expression. However, whether or not Twist2 has the same function in tumour metastasis remains unclear. The purpose of this study is to investigate the expressions and different roles of Twist1 and Twist2 in human hepatocellular carcinoma (HCC). The expressions of Twist1 and Twist2 in HCC tissue were evaluated by immunohistochemical staining. The role of Twist1 and Twist2 in invasiveness was also evaluated in vitro by using HCC cell lines. Twist1 nuclear overexpression is found to be correlated with HCC metastasis, and its expression is negatively correlated with E‐cadherin expression in human tissue. Twist2, a Twist1 homology protein, only expresses in the cytoplasm and shows no significant correlation with HCC metastasis. By ectopic transfection of Twist1 and Twist2 into the HCC cells, HepG2 and PLC, Twist1 is able to down‐regulate E‐cadherin expression and promote matrix metalloproteinase (MMP) activation, specifically in MMP2 and MMP9. In functional assays, Twist1 is found to promote invasion in HepG2 and PLC cells, but the invasion ability of the groups is not affected Twist2. Our findings indicate that Twist1 induces HCC invasion via increased activity in MMPs, leading to poor clinical prognoses. The results of this study also demonstrate a novel cogitation in Twist2, which has no effect on HCC invasion and metastasis. Twist1 may contribute to HCC invasion and metastasis and may be used as a novel therapeutic target for the inhibition of HCC metastasis. 相似文献
2.
3.
4.
5.
6.
TIPE1 suppresses invasion and migration through down‐regulating Wnt/β‐catenin pathway in gastric cancer
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Wenwen Liu Ye Chen Hua Xie Yongmin Guo Dandan Ren Yupeng Li Xu Jing Dongliang Li Xiao Wang Miaoqing Zhao Tianfeng Zhu Ziying Wang Xinbing Wei Fei Gao Xiaojie Wang Suxia Liu Yan Zhang Fan Yi 《Journal of cellular and molecular medicine》2018,22(2):1103-1117
Epithelial–mesenchymal transition (EMT) plays an important role in the invasiveness and metastasis of gastric cancer. Therefore, identifying key molecules involved in EMT will provide new therapeutic strategy for treating patients with gastric cancer. TIPE1 is a newly identified member of the TIPE (TNFAIP8) family, and its contributions to progression and metastasis have not been evaluated. In this study, we found that the levels of TIPE1 were significantly reduced and inversely correlated with differentiation status and distant metastasis in primary gastric cancer tissues. We further observed overexpression of TIPE1 in aggressive gastric cancer cell lines decreased their metastatic properties both in vitro and in vivo as demonstrated by markedly inhibiting EMT and metastasis of gastric cancer cells in nude mice. Consistently, gene silencing of TIPE1 in well‐differentiated gastric cancer cell line (AGS) inhibited these processes. Mechanistically, we found that TIPE1‐medicated Wnt/β‐catenin signalling was one of the critical signal transduction pathways that link TIPE1 to EMT inhibition. Importantly, TIPE1 dramatically restrained the expression and activities of MMP2 and MMP9 which are demonstrated to promote tumour progression and are implicated in EMT. Collectively, these findings provide new evidence for a better understanding of the biological activities of TIPE1 in progression and metastasis of gastric cancer and suggest that TIPE1 may be an innovative diagnostic and therapeutic target of gastric cancer. 相似文献
7.
The tumour suppressor OPCML promotes AXL inactivation by the phosphatase PTPRG in ovarian cancer
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jane Antony Elisa Zanini Zoe Kelly Tuan Zea Tan Evdoxia Karali Mohammad Alomary Youngrock Jung Katherine Nixon Paula Cunnea Christina Fotopoulou Andrew Paterson Sushmita Roy‐Nawathe Gordon B Mills Ruby Yun‐Ju Huang Jean Paul Thiery Hani Gabra Chiara Recchi 《EMBO reports》2018,19(8)
8.
9.
10.
Jing Teng Xiaoqian Wang Zhenxing Xu Nanhong Tang 《Journal of cellular biochemistry》2013,114(5):1097-1104
This study investigated the molecular mechanisms of liver cells with HBx expression on epithelium–mesenchymal transition (EMT) change using Western blot analysis and Transwell assay to assess EMT‐related protein expression and cell mobility. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were used to test the Twist promoter containing different STAT3 binding loci. Electrophoretic mobility band‐shift assay (EMSA) was used to detect Twist activity. Results showed that HBx expression affected the EMT‐related protein expression and the cell mobility of liver cancer cells (MHCC97) and liver cells (HL‐7702) in vitro or in vivo. These proteins exhibited reversed expression to a certain extent after Twist inhibition. In addition, the wound‐healing capability and the mobility of HL‐7702/HBx cells were lower than those treated with control‐siRNA. The expressions of p‐STAT3 and Twist were positively correlated with HBx expression. The second STAT‐3 binding sequence in the Twist promoter region of the HL‐7702/HBx cells was the first locus. Twist activity in the HL‐7702/HBx2 cells was higher than that in HL‐7702 cells. Moreover, the activity decreased when the cells were treated with HBx‐siRNA to inhibit HBx expression, or with STAT3 inhibitor to reduce STAT3 activation. Therefore, Twist is essential for the regulation of the mobility of liver cells with HBx expression. HBx activates the Twist promoter by activating STAT3 and promotes EMT occurrence in liver cells. J. Cell. Biochem. 114: 1097–1104, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
11.
Dandan Wu Zhongyuan Gao Ping Li Wenbin Huang Xuerong Wang 《Journal of cellular and molecular medicine》2017,21(12):3481-3493
Gastric cancer is the third leading cause of cancer‐related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte‐elevated gene‐1 (AEG‐1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG‐1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain‐ or loss‐of‐function of AEG‐1, respectively, promoted or suppressed epithelial–mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG‐1 positively regulated eIF4E, MMP‐9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG‐1‐regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP‐9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG‐1‐induced MMP‐9 and Twist. Finally, silencing of AEG‐1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP‐9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG‐1 promotes gastric cancer metastasis through upregulation of eIF4E‐mediated MMP‐9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis. 相似文献
12.
Danfang Zhang Baocun Sun Xiulan Zhao Huizhi Sun Jindan An Xian Lin Dongwang Zhu Xueming Zhao Xudong Wang Fang Liu Yanhui Zhang Jiameng Liu Qiang Gu Xueyi Dong Zhiqiang Qiu Zhiyong Liu Hong Qi Na Che Jing Li Runfen Cheng Xu Zheng 《Journal of cellular and molecular medicine》2020,24(13):7163-7174
The up‐regulation of EMT regulator Twist1 has been implicated in vasculogenic mimicry (VM) formation in human triple‐negative breast cancer (TNBC). Twist1 targets the Claudin15 promoter in hepatocellular carcinoma cells. Claudin family members are related with TNBC. However, the relationship between Claudin15 and VM formation is not clear. In this study, we first found that Claudin15 expression was frequently down‐regulated in human TNBC, and Claudin15 down‐regulation was significantly associated with VM and Twist1 nuclear expression. Claudin15 down‐regulation correlated with shorter survival compared with high levels. Claudin15 silence significantly enhanced cell motility, invasiveness and VM formation in the non‐TNBC MCF‐7 cells. Conversely, an up‐regulation of Claudin15 remarkably reduced TNBC MDA‐MB‐231 cell migration, invasion and VM formation. We also showed that down‐regulation of Claudin15 was Twist1‐dependent, and Twist1 repressed Claudin15 promoter activity. Furthermore, GeneChip analyses of mammary glands of Claudin15‐deficient mice indicated that Claudin18 and Jun might be downstream factors of Twist1‐Claudin15. Our results suggest that Twist1 induced VM through Claudin15 suppression in TNBC, and Twist1 inhibition of Claudin15 might involve Claudin18 and Jun expression. 相似文献
13.
Epithelial‐mesenchymal transition softens head and neck cancer cells to facilitate migration in 3D environments
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Yin‐Quan Chen Hsin‐Yi Lan Yi‐Chang Wu Wen‐Hao Yang Arthur Chiou Muh‐Hwa Yang 《Journal of cellular and molecular medicine》2018,22(8):3837-3846
The biological impact and signalling of epithelial‐mesenchymal transition (EMT) during cancer metastasis has been established. However, the changes in biophysical properties of cancer cells undergoing EMT remain elusive. Here, we measured, via video particle tracking microrheology, the intracellular stiffness of head and neck cancer cell lines with distinct EMT phenotypes. We also examined cells migration and invasiveness in different extracellular matrix architectures and EMT‐related signalling in these cell lines. Our results show that when cells were cultivated in three‐dimensional (3D) environments, the differences in cell morphology, migration speed, invasion capability and intracellular stiffness were more pronounced among different head and neck cancer cell lines with distinct EMT phenotypes than those cultivated in traditional plastic dishes and/or seated on top of a thick layer of collagen. An inverse correlation between intracellular stiffness and invasiveness in 3D culture was revealed. Knock‐down of the EMT regulator Twist1 or Snail or inhibition of Rac1 which is a downstream GTPase of Twist1 increased intracellular stiffness. These results indicate that the EMT regulators, Twist1 and Snail and the mediated signals play a critical role in reducing intracellular stiffness and enhancing cell migration in EMT to promote cancer cells invasion. 相似文献
14.
ZEB1‐mediated vasculogenic mimicry formation associates with epithelial–mesenchymal transition and cancer stem cell phenotypes in prostate cancer
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hua Wang Bin Huang Bai Mou Li Kai Yuan Cao Chen Qiang Mo Shuang Jian Jiang Jin Cheng Pan Zong Ren Wang Huan Yi Lin Dao Hu Wang Shao Peng Qiu 《Journal of cellular and molecular medicine》2018,22(8):3768-3781
The zinc finger E‐box‐binding homeobox 1 (ZEB1) induced the epithelial–mesenchymal transition (EMT) and altered ZEB1 expression could lead to aggressive and cancer stem cell (CSC) phenotypes in various cancers. Tissue specimens from 96 prostate cancer patients were collected for immunohistochemistry and CD34/periodic acid–Schiff double staining. Prostate cancer cells were subjected to ZEB1 knockdown or overexpression and assessment of the effects on vasculogenic mimicry formation in vitro and in vivo. The underlying molecular events of ZEB1‐induced vasculogenic mimicry formation in prostate cancer were then explored. The data showed that the presence of VM and high ZEB1 expression was associated with higher Gleason score, TNM stage, and lymph node and distant metastases as well as with the expression of vimentin and CD133 in prostate cancer tissues. Furthermore, ZEB1 was required for VM formation and altered expression of EMT‐related and CSC‐associated proteins in prostate cancer cells in vitro and in vivo. ZEB1 also facilitated tumour cell migration, invasion and clonogenicity. In addition, the effects of ZEB1 in prostate cancer cells were mediated by Src signalling; that is PP2, a specific inhibitor of the Src signalling, dose dependently reduced the p‐Src527 level but not p‐Src416 level, while ZEB1 knockdown also down‐regulated the level of p‐Src527 in PC3 and DU‐145 cells. PP2 treatment also significantly reduced the expression of VE‐cadherin, vimentin and CD133 in these prostate cancer cells. Src signalling mediated the effects of ZEB1 on VM formation and gene expression. 相似文献
15.
Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells
下载免费PDF全文
![点击此处可从《EMBO reports》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Tapan Kumar Mistri Arun George Devasia Lee Thean Chu Wei Ping Ng Florian Halbritter Douglas Colby Ben Martynoga Simon R Tomlinson Ian Chambers Paul Robson Thorsten Wohland 《EMBO reports》2015,16(9):1177-1191
16.
miR‐15b‐5p facilitates the tumorigenicity by targeting RECK and predicts tumour recurrence in prostate cancer
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ran Chen Lu Sheng Hao‐Jie Zhang Ming Ji Wei‐Qing Qian 《Journal of cellular and molecular medicine》2018,22(3):1855-1863
MicroRNAs (miRNAs) have been reported to participate in many biological behaviours of multiple malignancies. Recent studies have shown that miR‐15b‐5p (miR‐15b) exhibits dual roles by accelerating or blocking tumour progression. However, the molecular mechanisms by which miR‐15b contributes to prostate cancer (PCa) are still elusive. Here, miR‐15b expression was found significantly up‐regulated in PCa in comparison with the normal samples and was positively correlated with age and Gleason score in patients with PCa. Notably, PCa patients with miR‐15b high expression displayed a higher recurrence rate than those with miR‐15b low expression (P = 0.0058). Knockdown of miR‐15b suppressed cell growth and invasiveness in 22RV1 and PC3 cells, while overexpression of miR‐15b reversed these effects. Then, we validated that RECK acted as a direct target of miR‐15b by dual‐luciferase assay and revealed the negative correlation of RECK with miR‐15b expression in PCa tissues. Ectopic expression of RECK reduced cell proliferation and invasive potential and partially abrogated the tumour‐promoting effects caused by miR‐15b overexpression. Additionally, miR‐15b knockdown inhibited tumour growth activity in a mouse PCa xenograft model. Taken together, our findings indicate that miR‐15b promotes the progression of PCa cells by targeting RECK and represents a potential marker for patients with PCa. 相似文献
17.
Yang WH Lan HY Huang CH Tai SK Tzeng CH Kao SY Wu KJ Hung MC Yang MH 《Nature cell biology》2012,14(4):366-374
Epithelial-mesenchymal transition (EMT), which is characterized by the suppression of the adhesion protein E-cadherin, is a crucial process that promotes metastasis and stem-like properties of cancer cells. However, the dissociation of cellular aggregates is not sufficient to explain why cancer cells move, and the motile nature of cancer cells undergoing EMT remains elusive. Here, we identify a mechanism in which the EMT inducer Twist1 elicits cancer cell movement through activation of RAC1. Twist1 cooperates with BMI1 to suppress let-7i expression, which results in upregulation of NEDD9 and DOCK3, leading to RAC1 activation and enabling mesenchymal-mode movement in three-dimensional environments. Moreover, the suppression of let-7i contributes to Twist1-induced stem-like properties. Clinically, activation of the Twist1-let-7i-NEDD9 axis in head and neck cancer patients correlates with tumour invasiveness and worse outcome. Our results uncover an essential mechanism to explain how Twist1 induces the motile stem-like cancer cell phenotype beyond simply suppressing E-cadherin. 相似文献
18.
19.
20.
Mo Liu Jianguang Wang Hongzhang Huang Jingsong Hou Bin Zhang Anxun Wang 《Biochemical and biophysical research communications》2013
Although many researches have been undertaken to disclose the mechanisms of chemoresistance, the mechanisms remain unclear. The aim of this study is to elucidate the role of miR-181a–Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma (TSCC). We found that cisplatin-induced chemoresistance in TSCC cell lines underwent EMT (epithelial–mesenchymal transition) and was accompanied by enhancing metastatic potential (migration and invasion in vitro), miR-181a downregulation and Twist1 upregulation. Functional analyses indicated that miR-181a reversed chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Twist1 was confirmed as a direct miR-181a target gene by luciferase reporter gene assays. Twist1 knockdown by siRNA led to a reversal of the chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Our study demonstrates that miR-181a–Twist1 pathway may play an important role in the development of cisplatin-chemoresistance, with EMT and an increase the metastatic potential of TSCC cells. 相似文献