The ternary complex factor protein ELK1 is an independent prognosticator of disease recurrence in prostate cancer

Pardy, Luke; Rosati, Rita; Soave, Claire; Huang, Yanfang; Kim, Seongho; Ratnam, Manohar

doi:10.1002/pros.23932

Cited by 9 publications

(8 citation statements)

References 46 publications

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“…Moreover, expression of a hypo-ubiquitinated ELK-1 mutant, but not wild-type ELK-1, partially rescued the proliferation defect caused by USP17 depletion in HEK293T cells, illustrating the contribution of this mechanism towards mitogen signalling [ 86 ]. The established role for ELK-1 as an AR tethering element suggests that further studies are warranted to decipher whether USP17 acts on ELK-1 to promote tumorigenesis in PCa [ 91 , 92 , 93 ].…”

Section: Tcfs Showcase Mono-ubiquitination As a Non-destructive Mode Of Repressionmentioning

confidence: 99%

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ducker

Shaw

2021

IJMS

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Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers.

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Section: Tcfs Showcase Mono-ubiquitination As a Non-destructive Mode Of Repressionmentioning

confidence: 99%

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ducker

Shaw

2021

IJMS

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“…However, we have identified another PEA3 subfamily member, ETV1, to be expressed at high levels in low-grade glioma and decrease in expression in higher grades ( Figure 2 ). ELK-1 protein is known to be a critical partner for the androgen receptor (AR) in prostate cancer, and its expression was found to be associated with a higher clinical stage and prognostic marker of disease recurrence in prostate cancer [ 14 ]. No such distinction was apparent in our study on glioma grades 2–4.…”

Section: Discussionmentioning

confidence: 99%

“…T417 phosphorylation of Elk-1, a member of the ternary complex factor (TCF) subfamily, was found to be associated with the differentiation grade of colonic adenocarcinomas [ 13 ]. Additionally, in high clinical stage prostate cancer, ELK-1, not TCF members ELK3 or ELK4, was found to be associated with disease recurrence [ 14 ]. In fact, ELK1 expression was reported to be higher than ELK3 in many cancer cell lines, including brain, skin, and myeloid tumors and sarcomas [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma

Babal

Kandemir

Kurnaz

2021

JPM

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The ETS domain family of transcription factors is involved in a number of biological processes, and is commonly misregulated in various forms of cancer. Using microarray datasets from patients with different grades of glioma, we have analyzed the expression profiles of various ETS genes, and have identified ETV1, ELK3, ETV4, ELF4, and ETV6 as novel biomarkers for the identification of different glioma grades. We have further analyzed the gene regulatory networks of ETS transcription factors and compared them to previous microarray studies, where Elk-1-VP16 or PEA3-VP16 were overexpressed in neuroblastoma cell lines, and we identify unique and common regulatory networks for these ETS proteins.

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“…Phosphorylation of Elk-1 through MAPK/ERK signaling pathways activate TCF with serum response factor (SRF) and serum response elements to induce target gene transcription. Various studies showed that prostate cancer was influenced by Elk-1, before and after castration therapy [22], [23], [24]. The study of Patki et al reported that cooperative action of Elk-1 and AR did not involve phosphorylation of Elk-1, did not require SRF, and did not activate TCF.…”

Section: Discussionmentioning

confidence: 99%

“…Elk-1 was an independent risk factor for recurrence of prostate cancer along with clinical T-stage and prognostic grade. It warrants further detailed studies of the clinical utility of including Elk-1 with the currently used predictive signature of disease recurrence in prostate cancer [24]. Kawahara et al found the different result that no statistically significant correlation between p-Elk-1 expression and tumor grade (p = 0.810), but there was a trend toward significance between moderate-strong p-Elk-1 expression and worse patients outcomes [20].…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor and ETS-Like Protein-1 Expression of Prostate Cancer Correlates with Gleason Score International Society of Urological Pathology 2014/WHO 2016

Putriyuni

Tjong

Yanwirasti

et al. 2021

Open Access Maced J Med Sci

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AIM: Prostate cancer is the second most common and the fifth leading cause of death by cancer in men worldwide now. Grading based on Gleason score is a significant prognostic factor of prostate cancer. Androgen receptor (AR) plays important role in the initiation and progression of prostate cancer. AR signaling pathways in prostate cancer can also promote MAPK/ERK signaling pathways which activate ETS-like protein1 (Elk-1). METHODS: A total of 56 slides and paraffin blocks sampling of prostate cancer by consecutive from Department of Anatomical Pathology in West Sumatera. Hematoxylin and eosin (HE) stained slides were evaluated to review Gleason score, histopathological grading, and WHO grade group based on International Society of Urological Pathology (ISUP) 2014/WHO 2016. Immunohistochemistry staining of AR and Elk-1 was performed to analyze protein expression. RESULTS: Prostate cancers were found in mean age 70.68 ± 7.99 years. The most proportion of prostate cancer was Gleason score 9 (44.64%), histopathological grading poorly differentiated/undifferentiated (76.78%), and WHO grade Group 5 (48.21%). The positive expression AR of tumor cells 39 (69.64%) and Elk-1 34 (60.71%). Statistically, these results showed significant correlations of AR (p = 0.009) and Elk-1 (p = 0.012) with Gleason score. CONCLUSIONS: These results showed complex interactions between AR and Elk-1 initiation and progression of prostate cancer. Both variables indicated a significant correlation with Gleason score so that biomarkers prognostic potentially for prostate cancer.

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The ternary complex factor protein ELK1 is an independent prognosticator of disease recurrence in prostate cancer

Cited by 9 publications

References 46 publications

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development

Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma

Androgen Receptor and ETS-Like Protein-1 Expression of Prostate Cancer Correlates with Gleason Score International Society of Urological Pathology 2014/WHO 2016

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