An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to-mesenchymal transition (EMT) in colorectal cancer

Qin, Yong; Tang, Bo; Hu, C.; Xiao, Yufeng; Xie, Rui; Xin, Yong; Wu, Yu Yun; Dong, Hui; Yang, Shi‐Ming

doi:10.18632/oncotarget.5968

Cited by 74 publications

(71 citation statements)

References 37 publications

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“…At present, it is believed that tumor metastasis mainly includes the following steps: i) separation from primary lesions, in which cells undergo epithelial-to-mesenchymal transition (EMT) in order to detach; ii) cell invasion of surrounding tissues, in which cells penetrate the basement membrane and reach blood vessels or lymphatics, a process mediated by matrix metalloproteinases (MMPs) and proteolytic enzymes; iii) survival in the vasculature or lymphatic system; and iv) migration from the blood or lymph vessels, adhesion in distal tissues, and formation of micrometastatic nodes (19). Epithelial cells express E-cadherin to achieve intercellular adhesion, the expression of E-cadherin protein is increased, while the occurrence of EMT is decreased (20). This study has shown that the proliferation ability of tumor cells in the experimental group was weakened and the number of cells and migration ability were also decreased.…”

Section: Discussionmentioning

confidence: 99%

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Wang

2016

Oncology Letters

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The aim of the present study was to investigate the effect of aspirin on the cell proliferation and migration of gastric cancer cells in p53-knockout mice. Twenty p53−/− male mice aged 6 to 7 weeks, with an average weight of 20±3 g were used. The model of gastric cancer was established by the implantation of a mouse forestomach carcinoma cell line, subcutaneously, at the back of the neck, and then the mice were randomly divided into two groups after establishment of the model (control group, n=10; experimental group, n=10). Aspirin (250 mg/kg) was added to the food in the experimental group one day before model establishment, until the end of the experiment. Mice in the control group were given regular food without aspirin. All mice were sacrificed 3 months afterwards, and gastric cancer tissues were harvested. MTT assay was used to detect the proliferation of the tumor cells. Tumor cell number was also observed. Migration ability was detected by scratch assay, and E-cadherin protein expression was evaluated by immunofluorescence. The results revealed that the proliferation ability of tumor cells in the experimental group was lower than that in the control group. In addition, cell numbers were significantly decreased and the migration ability was diminished. The expression of E-cadherin was also increased in the experimental group, and the differences were statistically significant (P<0.05). In conclusion, aspirin inhibited the cell proliferation and migration of gastric cancer cells in mice.

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Section: Discussionmentioning

confidence: 99%

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Wang

2016

Oncology Letters

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“…NF-κB-dependent MMP expression likely contributes to changes in adhesive properties and increased invasiveness seen in cancer cells treated with telomerase template antagonists [117, 118]. Additionally, NF-κB acts synergistically with TGF-β to promote EMT and cancer cell dissemination [119, 120], while TERT enhances EMT stimulated by TGF-β by interacting directly with ZEB1, which suppresses E-cad expression [121, 122]. Taken together, these findings demonstrate that TERT functions at the center of an intricate transcriptional network that controls multiple regulators of metastasis.…”

Section: Telomerase: More Than a Telomere Machinementioning

confidence: 99%

“…), TERT uniquely functions in binding ZEB1 and amplifying EMT programs stimulated by TGF-β [121, 122]. TERT also interacts with NF-κB to enhance the production of MMPs, thereby promoting the liberation of carcinoma cells from the primary tumor en route to the systemic circulation [115, 116].…”

Section: Telomere Homeostasis: Determinant or Consequence Of Metasmentioning

confidence: 99%

Means to the ends: The role of telomeres and telomere processing machinery in metastasis

Robinson

Schiemann

2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Despite significant clinical advancements, cancer remains a leading cause of mortality throughout the world due largely to the process of metastasis and the dissemination of cancer cells from their primary tumor of origin to distant secondary sites. The clinical burden imposed by metastasis is further compounded by a paucity of information regarding the factors that mediate metastatic progression. Linear chromosomes are capped by structures known as telomeres, which dictate cellular lifespan in humans by shortening progressively during successive cell divisions. Although telomere shortening occurs in nearly all somatic cells, telomeres may be elongated via two seemingly disjoint pathways: (i) telomerase-mediated extension, and (ii) homologous recombination-based alternative lengthening of telomeres (ALT). Both telomerase and ALT are activated in various human cancers, with more recent evidence implicating both pathways as potential mediators of metastasis. Here we review the known roles of telomere homeostasis in metastasis and posit a mechanism whereby metastatic activity is determined by a dynamic fluctuation between ALT and telomerase, as opposed to the mere activation of a generic telomere elongation program. Additionally, the pleiotropic nature of the telomere processing machinery makes it an attractive therapeutic target for metastasis, and as such, we also explore the therapeutic implications of our proposed mechanism.

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“…4C). E-cadherin is one of the epithelial molecular markers that is always downregulated during EMT progression [27,28].…”

Section: Effects Of Fgf18 On the Expression Of Proliferation- Migratmentioning

confidence: 99%

FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling

Song

Zhong

et al. 2018

Cell Physiol Biochem

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Background/Aims: Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to autocrine and paracrine growth stimulation in several human malignant tumors, including breast cancer. However, the mechanisms underlying the carcinogenic actions of FGF18 remain unclear. Methods: The transcription level of FGF18 under the hypoxic condition was detected with quantitative PCR (qPCR). A wound-healing assay was performed to assess the role of FGF18 in cell migration. A clonogenicity assay was used to determine whether FGF18 silencing affected cell clonogenicity. Western blotting was performed to investigate Akt/GSK3β/β-catenin pathway protein expression. Binding of β-catenin to the target gene promoter was determined by chromatin immunoprecipitation (ChIP) assays. Results: FGF18 promoted the epithelial-mesenchymal transition (EMT) and migration in breast cancer cells through activation of the Akt/GSK3β/β-catenin pathway. FGF18 increased Akt-Ser473 and -Thr308 phosphorylation, as well as that of GSK3β-Ser9. FGF18 also enhanced the transcription of proliferation-related genes (CDK2, CCND2, Ki67), metastasis-related genes (TGF-β, MMP-2, MMP-9), and EMT markers (Snail-1, Snail-2, N-cadherin, vimentin, TIMP1). β-catenin bound to the target gene promoter on the ChIP assay. Conclusion: FGF18 contributes to the migration and EMT of breast cancer cells following activation of the Akt/GSK3β/β-catenin pathway. FGF18 expression may be a potential prognostic therapeutic marker for breast cancer.

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An hTERT/ZEB1 complex directly regulates E-cadherin to promote epithelial-to-mesenchymal transition (EMT) in colorectal cancer

Cited by 74 publications

References 37 publications

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice

Means to the ends: The role of telomeres and telomere processing machinery in metastasis

FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling

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