The function of the ELF3 gene and its mechanism in cancers

Ju, Yiheng; Fang, Sheng; Liu, Lei; Ma, Hui; Zheng, Longbo

doi:10.1016/j.lfs.2024.122637

Cited by 2 publications

(3 citation statements)

References 65 publications

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“…55 In the context of cancer, more recent studies showed that ELF3 controls processes of epithelial-mesenchymal-transition and thereby impacts tumor features such as migration and invasion. 37,56,57 In line, with these observations our experiments demonstrate that ELF3 expression recapitulates the impaired migratory mode of ANXA4 knockout cells (Figure 7). These findings might be explained by a potential EMT-promoting effect of ANXA4, as it was also recently demonstrated for ANXA10 in cholangiocarcinoma.…”

Section: Discussionsupporting

confidence: 86%

“…E74-like factor 3 (ELF3) is involved in various cellular processes ranging from epithelial differentiation to modulation of cytokines, and has been shown to exert context-dependent roles either as a tumor-suppressor or even more oncogene-like functions in various malignancies. 37 Taken together, our observations imply ANXA4-dependent altered transcriptional signatures involving matrisomal- and immune-related genes, and led to the identification of the transcription factor ELF3 as a potential regulator of relevant gene sets.…”

Section: Resultsmentioning

confidence: 63%

“…Together, these observations imply that ELF3 suppresses invasive migratory modes in line with its known role as a potential tumor suppressor and counter-acting transcription factor of EMT. 37 Further co-expression analysis of ELF3 employing the TCGA ccRCC database revealed ELF3 co-regulated gene signatures (intersectional analysis with Immunome, EMTome and Matrisome), where secreted chemokine factors (e.g. CCL2, CXCL1, CXCL6) were identified (Figure 7l and Supplementary Spreadsheet S7).…”

Section: Resultsmentioning

confidence: 99%

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Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

Wess,

Rogg,

Gueib-Picard

et al. 2024

Preprint

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Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of renal malignant disease and is characterized by dismal prognosis in the metastasized setting. Invasive growth of cancer cells relates to high levels of compressive forces translating to relevant damage of the plasma membrane. However, functional implications of protein machineries required for plasma membrane repair in ccRCC are not yet completely elucidated. Given the membrane-associated localization of the large family of annexin proteins, we aimed for a global annotation of annexin proteins, which led to the identification of ANXA4 selectively expressed in cancer cells of ccRCC. Interestingly, ANXA4 showed context-dependent distinct localization patterns including the plasma membrane as well as the nuclear compartment/nuclear membrane. We investigated the functional role of ANXA4 in ccRCC employing genetic titration studies (knockdown, CRISPR/Cas9 knockout and overexpression) and identified impaired acute plasma membrane repair as well as invasive capability in conditions of reduced ANXA4 expression. Utilizing computational segmentation of the tumor microenvironment (TME) of ccRCC samples revealed that ANXA4 low tumors exhibited a distinct TME composition compared to ANXA4 high cases. ANXA4 low tumors showed higher levels of tumor infiltrating lymphocytes accompanied by increased deposition of acellular extracellular matrix. Further transcriptomic analysis demonstrated major alterations in transcriptional signatures related to epithelial-mesenchymal transition (EMT) and immune signaling. Transcription factor enrichment analysis and further functional validation identified ELF3 as one central regulator of invasive properties. Our integrative approach including molecular analyses with advanced histopathological segmentation uncovered novel roles for ANXA4 in modulating acute membrane repair, transcriptional regulation, and shaping cellular composition of the ccRCC tumor microenvironment.

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Section: Discussionsupporting

confidence: 86%

Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

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Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

Wess,

Rogg,

Gueib-Picard

et al. 2024

Preprint

View full text Add to dashboard Cite

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Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy

Huang,

Wen,

2024

Front. Pharmacol.

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Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied transcription factor, mediates multiple malignant behaviors by regulating cell cycle progression, tumor metastasis, and therapeutic response. Emerging evidence suggests that lncRNAs play a pivotal role in regulating the E2F1 pathway. This review aims to elucidate the intricate gene regulatory programs between lncRNAs and E2F1 in cancer progression. We elaborate on distinct mechanistic networks involved in cancer progression, emphasizing the potential of the lncRNAs/E2F1 axes as promising targets for cancer therapy. Additionally, we provide novel perspectives on current evidence, limitations, and future directions for targeting lncRNAs in human cancers. Fully deciphering the intricate network of lncRNA/E2F1-mediated regulatory mechanisms in cancer could facilitate the translation of current findings into clinical course, such efforts ultimately significantly improve the clinical prognosis of cancer patients.

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The function of the ELF3 gene and its mechanism in cancers

Cited by 2 publications

References 65 publications

Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy

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