E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms

Jiang, Wenxiao; Xu, Yichi; Chen, Xin; Pan, Shuya; Zhu, Xueqiong

doi:10.1016/j.omto.2021.07.012

Cited by 11 publications

(10 citation statements)

References 89 publications

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“…In COAD, ETV4 was the most highly upregulated gene compared to normal tissues. Recently, this transcription factor was shown to be critical for cancer growth and was positively correlated with poor prognosis in cancer patients 40,41 . In terms of metabolism, ETV4 activates PPARγ signaling 42 , which directly regulated glycolysis and fatty acid metabolism in cancer cells 43,44 .…”

Section: Discussionmentioning

confidence: 99%

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer

Kim

Shin

Jung

et al. 2023

Preprint

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Gastrointestinal malignancies such as colon adenocarcinoma (COAD) and liver hepatocellular carcinoma (LIHC) are the major causes of cancer-related deaths worldwide. Identifying the common genetic foundations and signaling pathways among these cancers can lead to improved understanding of their underlying mechanisms and potential therapeutic targets. Here, we tried to identify differentially expressed genes (DEGs) and enriched pathways associated with tumorigenesis using publicly accessible the Cancer Genome Atlas datasets of COAD and LIHC. Our analysis revealed that DEGs during early tumorigenesis were associated with various aspects of cell cycle regulation. Genes related to lipid metabolism were significantly enriched in COAD and LIHC, suggesting that dysregulated lipid metabolism may play a crucial role in the development and progression of COAD and LIHC. A subset of DEGs associated with mitochondrial function and structure was identified, among which genes involved in mitochondrial protein import and mitochondrial respiratory complex assembly were upregulated in both cancers. We identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) as a crucial regulator of cancer cell metabolism. Using a genome-scale metabolic model, we showed that HMGCS2 suppression increased glycolysis, lipid biosynthesis and elongation, and decreased fatty acid oxidation in colon cancer cells. Overall, the present study highlights the potential contribution of dysregulated lipid metabolism, including ketogenesis, to the development and progression of COAD and LIHC. These findings could prove vital for developing targeted therapies for these malignancies and pave the way for more effective treatments.

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Section: Discussionmentioning

confidence: 99%

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer

Kim

Shin

Jung

et al. 2023

Preprint

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“…Our study prompts a revision into the crosstalk between ERK, WNT, BMP and DNA methylation driving lineage switching in colorectal cancer [62][63][64][65] . We propose that a better strategy would include targeting uniquely expressed ETS [66][67][68][69] or PBX proteins 42 modulating ERK levels shaping the oncogenic methylome.…”

Section: Discussionmentioning

confidence: 99%

Differential ERK activity shapes the epiblast methylome influencing cell-context response to germ-layer differentiation signals.

Ferretti

Menezes

Peterson

et al. 2023

Preprint

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Stem cells hold promise in regenerative medicine as they have the potency to differentiate into a variety of specialized cell types. However, mechanisms underlying stem cell plasticity and lineage acquisition remain elusive. Epigenetic modifications and genome accessibility prime cellular feedback to signalling cues affecting differentiation plasticity and cell fate acquisition. Deciphering how this epigenetic code influences the context-dependent response of pluripotent cells to differentiation cues will elucidate how mammalian tissue diversity is established. Using ERK-deficient in vitro and in vivo models, we show that ERK-driven lineage-specific epigenetic signatures precede transcriptional activation of germ layer differentiation programs. We provide evidence that while distinct chromatin accessibility and methylome states prime BMP-dependent fate decisions, DNA methylation but not chromatin accessibility safeguards WNT response in the epiblast. This study establishes that ERK-driven epigenetic machinery balances epiblast plasticity and canalization, allowing context-specific spatiotemporal responses to promiscuously used signalling cues controlling organogenesis and cancers.

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“…ETV4 overexpression was observed in various cancer types, such as prostate cancer, bladder cancer, gastric cancer, colon cancer, and hepatocellular carcinoma, and the underlying mechanism and oncogenic function have been revealed, which suggest the importance of ETV4 in cancer research [ 35 ]. Therefore, our study will help to advance and accelerate the understanding ETV4 -associated human cancers.…”

Section: Discussionmentioning

confidence: 99%

Portrait of Molecular Signaling and Putative Therapeutic Targets in Prostate Cancer with ETV4 Fusion

2022

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Gene fusion between androgen receptor (AR) response genes and E26 transformation-specific (ETS) family members increases the gene expression of ETS family members, and promotes tumorigenesis in prostate cancer. However, the molecular features of ETV4 fusion in prostate cancer are not fully understood, and drugs targeting ETV4 fusion have not been developed. To examine key cellular signaling pathways and explore therapeutic targets and drugs for ETV4-fusion-positive prostate cancer, we analyzed RNA sequencing data and clinical information for prostate cancer. The ETV4-fusion-positive group was selected through prior study and analysis comparing ETV4-fusion-positive and -negative groups was conducted using a Pearson correlation test. We obtained 393 genes correlated with ETV4 expression. Pathway analysis was performed using over-representation analysis (ORA), and six cancer-specific molecular signaling pathways (the irinotecan pathway, metabolism, androgen receptor signaling, interferon signaling, MAPK/NF-kB signaling, and the tamoxifen pathway) were altered in the ETV4-fusion-positive group. Furthermore, a gene–drug database was used to find an actionable drug and therapeutic target for the ETV4-fusion-positive group. Here, we have identified significantly altered genes and oncogenic signaling pathways in ETV4-fusion-positive prostate cancer, and we suggest therapeutic targets and potential drugs for ETV4-fusion-positive prostate patients.

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E26 transformation-specific variant 4 as a tumor promotor in human cancers through specific molecular mechanisms

Cited by 11 publications

References 89 publications

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer

Differential ERK activity shapes the epiblast methylome influencing cell-context response to germ-layer differentiation signals.

Portrait of Molecular Signaling and Putative Therapeutic Targets in Prostate Cancer with ETV4 Fusion

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