GTSE1 promotes cell migration and invasion by regulating EMT in hepatocellular carcinoma and is associated with poor prognosis

Wu, Xiaojuan; Wang, Hongbo; Lian, Yifan; Chen, Lubiao; Gu, Lin; Wang, Jialiang; Huang, Yanlin; Deng, Meihai; Gao, Zhiliang; Huang, Yuehua

doi:10.1038/s41598-017-05311-2

Cited by 51 publications

(50 citation statements)

References 31 publications

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“…Slug, a zinc finger transcription factor, has been proposed as a key EMT inducer affecting melanoma metastatic propensity . A study of hepatocellular carcinoma also showed that GTSE1 depletion had a significant impact on EMT, causing decreased expression of Snail, N‐Cadherin, and β‐catenin and decreased metastatic potential . In our data, decreased Slug occurred concomitantly with the cadherin switch and migration attenuation.…”

Section: Discussionsupporting

confidence: 70%

“…G2 and S‐phase expressed 1 (GTSE1) has been found expressed only in the S and G2 phases of the cell cycle, where it colocalized with tubulin and microtubules, and is overexpressed in lung cancer, breast cancer, and liver cancer . Accumulating evidence indicates that GTSE1 correlates with tumor metastasis and poor clinical outcome in neuroblastoma, neuroendocrine tumors, oral tongue squamous cell carcinoma, and hepatocellular carcinoma . In response to DNA damage, GTSE1 accumulates in the nucleus, where it downregulates p53 and represses its ability to induce apoptosis .…”

Section: Introductionmentioning

confidence: 99%

“…24 Accumulating evidence indicates that GTSE1 correlates with tumor metastasis and poor clinical outcome in neuroblastoma, 25 neuroendocrine tumors, 26 oral tongue squamous cell carcinoma, 27 and hepatocellular carcinoma. 24 In response to DNA damage, GTSE1 accumulates in the nucleus, where it downregulates p53 and represses its ability to induce apoptosis. [28][29][30] Negative regulation of p53 allows cells to resist apoptosis and transition through the G2/M checkpoint, leading to tumor progression.…”

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confidence: 99%

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High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

Chen

et al. 2018

Cancer Science

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G2 and S‐phase expressed 1 (GTSE1) regulates cell cycle progression in human cancers. However, its significance and mechanism of action in acral melanoma (AM) remain unknown. In the present study, we found that GTSE1 expression was upregulated in advanced stage/metastatic AM tissues and metastatic cell lines, and correlated with higher stage (P = .028) and poor disease‐free survival (DFS) in patients with AM (P = .003). Cox regression assays validated GTSE1 expression to be an independent prognostic factor of DFS for patients with AM (P = .004). Ectopic expression of GTSE1 enhanced primary AM cell proliferation, invasion, and migration. Loss‐of‐function in GTSE1 attenuated metastatic AM cell proliferation and metastatic ability in vitro and in vivo. We additionally observed that inhibition of migration and invasion occurred concomitantly with a GTSE1 knockdown‐mediated increase in E‐cadherin and decreases in N‐cadherin and Slug. We further showed that integrin subunit alpha 2 (ITGA2) interacts with GTSE1 and is a downstream effector of GTSE1. Further, ITGA2 levels were positively correlated with GTSE1 expression in human AM tissues. Ectopic ITGA2 expression rescued siGTSE1‐mediated inhibition of migration and invasion, thereby restoring epithelial‐to‐mesenchymal transition (EMT). In conclusion, GTSE1 expression promotes AM progression and correlates with clinical outcomes of patients with AM, and may represent a promising therapeutic target to suppress AM progression.

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Section: Discussionsupporting

confidence: 70%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

Chen

et al. 2018

Cancer Science

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“…N-cadherin, a homophilic transmembrane adhesion glycoprotein, acts as a transmembrane signal transduction receptor influencing cell-cell adhesion and therefore serves a role in invasion and migration during cancer progression (37)(38)(39). Accumulating evidence suggests that N-cadherin is implicated in promoting cancer cell motility (40), thyroid tumorigenesis (41), migration and invasion (42). One report suggests that N-cadherin serves a prognostic role in patients with BC (43).…”

Section: Discussionmentioning

confidence: 99%

microRNA‑145 modulates migration and invasion of bladder cancer cells by targeting N‑cadherin

Zhang

Chang

et al. 2018

Mol Med Report

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MicroRNA (miRNA)‑145 has been demonstrated to serve a role in several types of tumors, however, the potential molecular mechanism of action of miRNA‑145 in bladder cancer metastasis remains to be elucidated. This study aimed to investigate the potential modulation of miRNA‑145 in bladder carcinoma and elucidate the underlying molecular mechanism. The expression of miRNA‑145 in bladder adenocarcinoma tissues and bladder cancer cells was measured by reverse transcription‑quantitative polymerase chain reaction. miRNA‑145 mimics and inhibitor were transfected into bladder cancer (BC) cells to determine the role of miRNA‑145 on cell motility and invasion measured by wound healing and transwell assays. Luciferase assay was performed to confirm whether N‑cadherin was the direct target of miRNA‑145. Subsequently, expression of N‑cadherin and matrix metalloproteinase‑9 (MMP9) in BC cells were detected by western blot analysis. miRNA‑145 was significantly downregulated cells and tissues from patients with BC, compared with healthy controls. miRNA‑145 markedly inhibited the ability of BC cells to migrate and invade. Furthermore, N‑cadherin was identified as a target of miRNA‑145 in BC cells. MMP9, acting downstream of N‑cadherin, was downregulated in BC cells by miRNA‑145. In the present study, miRNA‑145 suppressed the migration and invasion of BC cells by regulating N‑cadherin. The results of the present study indicated that miRNA‑145 may function as a tumor suppressor and may have a potential to be a diagnostic and predictive biomarker, and a therapeutic target for treatment of BC.

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“…We selected GTSE1, NMU, FOS and CDKN1C for further research through PPI network analysis because they are the core genes. It has been reported that GTSE1 is highly expressed in tumors such as liver cancer and melanoma, and is associated with poor prognosis of patients [18,19]. Moreover, GTSE1 may be involved in tumorigenesis and progression by regulating p53 phosphorylation [20,21].…”

Section: Gepia Analysismentioning

confidence: 99%

Screening prognostic markers for non-small cell lung cancer based on data mining and bioinformatics analysis

Han¹,

Aman²,

Wei³

et al. 2020

Preprint

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Background At present, non-small cell lung cancer has a high morbidity and mortality, and the recurrence and metastasis situation is serious. It is impossible to accurately predict the prognosis of cancer patients clinically. Biomarker is a kind of biomolecule with wide application prospects, and its potential in cancer prognosis is gradually revealed, and it is expected to be applied clinically. Results We integrated four gene expression profiles (GSE19188, GSE19804, GSE101929 and GSE18842) from the GEO database and screened the commonly differentially expressed genes using the GEO2R online tool. We screened 952 commonly differentially expressed genes. Gene ontology analysis showed that CDEGs were mainly enriched in biological processes such as cell adherin, angiogenesis and positive regulation of angiogenesis, and KEGG pathways such as ECM-receptor interaction and cell adherin molecules (CAMs). Up-regulation of G2 and S phase-expressed protein 1(GTSE1) expression is associated with poor prognosis of lung adenocarcinoma(LADE) and lung squamous cell carcinoma(LUSC). Up-regulation of Neuromedin-U(NMU) expression, down-regulation of Proto-oncogene c-Fos(FOS) and Cyclin-dependent kinase inhibitor 1C(CDKN1C) is only associated with poor prognosis of LADE. Conclusions We believe that GTSE1, NMU, FOS, and CDKN1C have potential application value as prognostic markers for lung adenocarcinoma, and are of great significance for lung adeno carcinoma efficacy evaluation and relapse monitoring. At the same time, GTSE1 may also be used as a new target for cancer treatment New ways.

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GTSE1 promotes cell migration and invasion by regulating EMT in hepatocellular carcinoma and is associated with poor prognosis

Cited by 51 publications

References 31 publications

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

High G2 and S‐phase expressed 1 expression promotes acral melanoma progression and correlates with poor clinical prognosis

microRNA‑145 modulates migration and invasion of bladder cancer cells by targeting N‑cadherin

Screening prognostic markers for non-small cell lung cancer based on data mining and bioinformatics analysis

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