Strong cytoplasmic ETV1 expression has a negative impact on prostate cancer outcome

Segalés, Laura; Juanpere, Núria; Lorenzo, Marta; Albero-González, Raquel; Fumadó, Lluís; Cecchini, L.; Bellmunt, Joaquim; Lloreta‐Trull, Josep; Hernández‐Llodrà, Silvia

doi:10.1007/s00428-019-02573-1

Cited by 4 publications

(4 citation statements)

References 34 publications

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“…Besides, authors have reported its clinical significance. High ETV1 levels are correlated with shorter prostatespecific antigen (PSA) recurrence in prostate cancer, while nuclear overexpression of ETV1 is associated with longer overall survival in esophageal adenocarcinoma [47,48]. Functionally, ETV1 influences tumor progression by inducing EMT, promoting cell migration and invasion, regulating cell cycle and apoptosis, as well as mediating chemotherapy resistance [12].…”

Section: Discussionmentioning

confidence: 99%

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

Zhang

Wang

Xie

et al. 2022

J Exp Clin Cancer Res

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Background: Metastasis is a major determinant of death in patients with hepatocellular carcinoma (HCC). Dissecting key molecular mediators that promote this malignant feature may help yield novel therapeutic insights. Here, we investigated the role of E-twenty-six transformation-specific variant 1 (ETV1), a member of the E-twenty-six transformation-specific (ETS) family, in HCC metastasis. Methods:The clinical significance of ETV1 and its target genes in two independent cohorts of HCC patients who underwent curative resection were assessed by Kaplan-Meier analysis and Multivariate Cox proportional hazards model. Luciferase reporter assay and chromatin immunoprecipitation assay were used to detect the transcriptional regulation of target gene promoters by ETV1. The effect of ETV1 on invasiveness and metastasis of HCC were detected by transwell assays and the orthotopically metastatic model.Results: ETV1 expression was frequently elevated in human HCC specimens. Increased ETV1 expression was associated with the malignant biological characteristics and poor prognosis of HCC patients. ETV1 facilitated invasion and metastasis of HCC cells in vitro and in vivo. Mechanistically, ETV1 promoted HCC metastasis via upregulating metastasis-related genes, including protein tyrosine kinase 2 (PTK2) and MET. Down-regulated the expression of PTK2 or tyrosine protein kinase Met (c-MET) decreased ETV1-mediated HCC metastasis. Hepatocyte growth factor (HGF) upregulated ETV1 expression through activating c-MET-ERK1/2-ELK1 pathway. Notably, in two independent cohorts, patients with positive coexpression of ETV1/PTK2 or ETV1/c-MET had worse prognosis. Furthermore, the combination of PTK2 inhibitor defactinib and c-MET inhibitor capmatinib significantly suppressed HCC metastasis induced by ETV1.

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Section: Discussionmentioning

confidence: 99%

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

Zhang

Wang

Xie

et al. 2022

J Exp Clin Cancer Res

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“…The PEA3 subgroup contains three transcription factors: ETV1 (ER81), ETV4 (PEA3/E1AF), and ETV5 (ERM) [ 7 ]. Studies have shown that ETV1, ETV4, and ETV5 are overexpressed in a variety of tumors [ 19 – 21 ]. The high level of expression of these transcription factors usually leads to more aggressive and drug-resistant tumors.…”

Section: Discussionmentioning

confidence: 99%

“…As a member of the PEA3 subfamily of the ETS family, ETV5 and other PEA3 subfamily members play a carcinogenic role in tumors and are independent poor prognostic factors. Segalés L et al reported that ETV1 transcription factor is highly expressed in prostate cancer, and that high mRNA level of ETV1 is associated with the short recurrence time of prostate-specific antigen [ 19 ]. In CRC, the expression of ETV4 mRNA is significantly high, and it is significantly positively correlated with the depth of invasion, lymph node metastasis, and tumor progression, suggesting that ETV4 can be used as a prognostic marker for CRC progression and metastasis [ 20 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

Biological and prognostic value of ETV5 in high-grade serous ovarian cancer

Zhang

Liu

et al. 2021

J Ovarian Res

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Background ETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates. Results Bioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p < 0.05). qRT-PCR showed that ETV5 was significantly overexpressed in HGSOC tissues than in fallopian tube tissues (p < 0.05). qRT-PCR and western blotting assays demonstrated that ETV5 was relatively highly expressed in OC cell lines. ETV5 overexpression was positively associated with poor survival in HGSOC patients, therefore making it a high-risk factor for HGSOC progression. Furthermore, ETV5 promoted the proliferation, migration, and invasion capabilities of HGSOC cells. Conclusion ETV5 has a carcinogenic effect in HGSOC and can be used as a clinically effective biomarker to determine the prognosis of HGSOC patients.

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“…This overexpression may have been attributable to epigenetics or cryptic translocations. Overexpression of ETV1 , but not ETV4 , is associated with reduced time to PSA recurrence post‐radical prostatectomy [74]. In another study of Chinese patients, ETV4 overexpression conferred worse survival [75].…”

Section: Prostate Cancermentioning

confidence: 99%

The genetic landscapes of urological cancers and their clinical implications in the era of high‐throughput genome analysis

2020

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Objective With the advent of high‐throughput genome analysis, we are increasingly able to sequence and hence understand the pathogenic processes underlying individual cancers. Recently, consortiums such as The Cancer Genome Atlas (TCGA) have performed large‐scale projects to this end, providing significant amounts of information regarding the genetic landscapes of several cancers. Patients and Methods We performed a narrative review of studies from the TCGA and other major studies. We aimed to summarise data exploring the clinical implications of specific genetic alterations, both prognostically and therapeutically, in four major urological cancers. These were renal cell carcinoma, muscle‐invasive bladder cancer/carcinoma, prostate cancer, and testicular germ cell tumours. Results With these four urological cancers, great strides have been made in the molecular characterisation of tumours. In particular, recent studies have focussed on identifying molecular subtypes of tumours with characteristic genetic alterations and differing prognoses. Other prognostic alterations have also recently been identified, including those pertaining to epigenetics and microRNAs. In regard to treatment, numerous options are emerging for patients with these cancers such as including immune checkpoint inhibition, epigenetic‐based treatments, and agents targeting MAPK, PI3K, and DNA repair pathways. There are a multitude of trials underway investigating the effects of these novel agents, the results of which are eagerly awaited. Conclusions As medicine chases the era of personalised care, it is becoming increasingly important to provide individualised prognoses for patients. Understanding how specific genetic alterations affects prognosis is key for this. It will also be crucial to provide highly targeted treatments against the specific genetics of a patient’s tumour. With work performed by the TCGA and other large consortiums, these aims are gradually being achieved. Our review provides a succinct overview of this exciting field that may underpin personalised medicine in urological oncology.

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Strong cytoplasmic ETV1 expression has a negative impact on prostate cancer outcome

Cited by 4 publications

References 34 publications

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

HGF-mediated elevation of ETV1 facilitates hepatocellular carcinoma metastasis through upregulating PTK2 and c-MET

Biological and prognostic value of ETV5 in high-grade serous ovarian cancer

The genetic landscapes of urological cancers and their clinical implications in the era of high‐throughput genome analysis

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