Decreased expression of EFS is correlated with the advanced prostate cancer

Sertkaya, Selda; Hamid, Syed Muhammad; Dilsiz, Nihat; Varisli, Lokman

doi:10.1007/s13277-014-2703-5

Cited by 11 publications

(13 citation statements)

References 32 publications

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“…EFS is a member of the CAS family proteins that is commonly downregulated in prostate cancers and has been described as a tumor suppressor . Loss of EFS expression, as a consequence of CpG sites hypermethylation, increases prostate cancer aggressiveness, a finding also made in uveal melanoma, particularly at a metastatic stage . Our findings suggest that the enhancement of aggressiveness could also occur in HNSCC, in which we found an association between low EFS expression and poor outcome (node 1 patients).…”

Section: Discussionsupporting

confidence: 69%

“…[44][45][46] Loss of EFS expression, as a consequence of CpG sites hypermethylation, increases prostate cancer aggressiveness, a finding also made in uveal melanoma, particularly at a metastatic stage. 45,47 Our findings suggest that the enhancement of aggressiveness could also occur in HNSCC, in which we found an association between low EFS expression and poor outcome (node 1 patients). Loss of EFS expression could be important to activate the tumor immune system evasion, as EFS has a key role in T-cell lymphocyte function and maturation.…”

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

et al. 2019

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Background We aimed at identifying molecular markers predictive of clinical outcome in patients with head and neck cancer based on the expression profile of cells showing epithelial‐like (EL) or mesenchymal‐like (ML) phenotypes. Materials and methods We analyzed the association between EL and ML cells and migration, drug resistance, or tumor growth. The differential gene expression profile between cell types was used to build a model to stratify patients according to survival. Results EL cells were sensitive to cisplatin and cetuximab, showed low migration, and generated squamous differentiated tumors in mouse. A differential 93‐gene expression signature between ML and EL cells was used to build a three‐gene (EFS, GPX2, and SPRR1A) survival model by analyzing the RNA‐seq data of the TCGA‐HNSC project. Its prognostic value was confirmed in two independent cohorts. Conclusion EFS, GPX2, and SPRR1A are prognostic markers able to distinguish clinical outcome among subtypes sharing an EL phenotype.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 83%

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The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

et al. 2019

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“…Further investigation indicated that methylation of CpG sites that is specifically predicted to result in reduction of gene expression was restricted to the FLNC and EFS genes (p ≤ .03), both involved in cell attachment [87]. In a study conducted by Marques et al, EFS expression was strongly downregulated in hormonal therapy-resistant versus therapy-responsive PC346C prostate cancer cells [88], in general agreement with a second study, in which low EFS expression correlated with malignant behavior of the PC-3 and LNCaP prostate cancer cells [89]. Additional work showed decreased EFS mRNA expression levels in prostate cancer samples with higher Gleason scores [90].…”

Section: Implication Of Efs and Cass4 In Other Disorderssupporting

confidence: 61%

Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members

Deneka

Korobeynikov

Golemis

2015

Gene

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The CAS (Crk-associated substrate) adaptor protein family consists of four members: CASS1/BCAR1/p130Cas, CASS2/NEDD9/HEF1/Cas-L, CASS3/EFS/Sin and CASS4/HEPL. While CAS proteins lack enzymatic activity, they contain specific recognition and binding sites for assembly of larger signaling complexes that are essential for cell proliferation, survival, migration, and other processes. All family members are intermediates in integrin-dependent signaling pathways mediated at focal adhesions, and associate with FAK and SRC family kinases to activate downstream effectors regulating the actin cytoskeleton. Most studies of CAS proteins to date have been focused on the first two members, BCAR1 and NEDD9, with altered expression of these proteins now appreciated as influencing disease development and prognosis for cancer and other serious pathological conditions. For these family members, additional mechanisms of action have been defined in receptor tyrosine kinase (RTK) signaling, estrogen receptor signaling or cell cycle progression, involving discrete partner proteins such as SHC, NSP proteins, or AURKA. By contrast, EFS and CASS4 have been less studied, although structure-function analyses indicate they conserve many elements with the better-known family members. Intriguingly, a number of recent studies have implicated these proteins in immune system function, and the pathogenesis of developmental disorders, autoimmune disorders including Crohn’s Disease, Alzheimer’s Disease, cancer, and other diseases. In this review, we summarize the current understanding of EFS and CASS4 protein function in the context of the larger CAS family group.

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“…We showed that just a few genes in each pattern were associated with both hypomethylated and hypermethylated probes, indicating the robustness of the identified groups of genes. For our top ten UPUP-only and UPDOWN-only genes, EFS and SPARCL1 from the UPDOWN-only group have previously been shown to be suppressed in PCa [45,46]. In another study, promoter hypermethylation and its negative correlation with the gene expression was demonstrated for genes TMEM106A and SCGB3A1 [47].…”

Section: Discussionmentioning

confidence: 58%

DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation

2020

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Background: Prostate cancer (PCa) has the highest incidence rates of cancers in men in western countries. Unlike several other types of cancer, PCa has few genetic drivers, which has led researchers to look for additional epigenetic and transcriptomic contributors to PCa development and progression. Especially datasets on DNA methylation, the most commonly studied epigenetic marker, have recently been measured and analysed in several PCa patient cohorts. DNA methylation is most commonly associated with downregulation of gene expression. However, positive associations of DNA methylation to gene expression have also been reported, suggesting a more diverse mechanism of epigenetic regulation. Such additional complexity could have important implications for understanding prostate cancer development but has not been studied at a genome-wide scale. Results: In this study, we have compared three sets of genome-wide single-site DNA methylation data from 870 PCa and normal tissue samples with multi-cohort gene expression data from 1117 samples, including 532 samples where DNA methylation and gene expression have been measured on the exact same samples. Genes were classified according to their corresponding methylation and expression profiles. A large group of hypermethylated genes was robustly associated with increased gene expression (UPUP group) in all three methylation datasets. These genes demonstrated distinct patterns of correlation between DNA methylation and gene expression compared to the genes showing the canonical negative association between methylation and expression (UPDOWN group). This indicates a more diversified role of DNA methylation in regulating gene expression than previously appreciated. Moreover, UPUP and UPDOWN genes were associated with different compartments-UPUP genes were related to the structures in nucleus, while UPDOWN genes were linked to extracellular features. Conclusion: We identified a robust association between hypermethylation and upregulation of gene expression when comparing samples from prostate cancer and normal tissue. These results challenge the classical view where DNA methylation is always associated with suppression of gene expression, which underlines the importance of considering corresponding expression data when assessing the downstream regulatory effect of DNA methylation.

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Decreased expression of EFS is correlated with the advanced prostate cancer

Cited by 11 publications

References 32 publications

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

The combined use of EFS, GPX2, and SPRR1A expression could distinguish favorable from poor clinical outcome among epithelial‐like head and neck carcinoma subtypes

Embryonal Fyn-associated substrate (EFS) and CASS4: The lesser-known CAS protein family members

DNA hypermethylation associated with upregulated gene expression in prostate cancer demonstrates the diversity of epigenetic regulation

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