ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT

Lv, Chunwei; Yu, Hongfei; Wang, Keyi; Chen, Chaoyi; Tang, Jinlong; Han, Fengyan; Mai, Minglang; Ye, Kehong; Lai, Maode; Zhang, Honghe

doi:10.3390/cells11152363

Cited by 24 publications

(14 citation statements)

References 39 publications

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“…We hypothesized that the ENO2-mediated glycolysis process might play a crucial role in supplying energy for anoikis resistance in ATC cells. Previous studies have shown that ENO2 is significantly involved in the development of various tumors ( 22 , 28 , 53 ), prompting our assumption that regulating ENO2 expression might influence the fate of cells under detached culture conditions. Our in vitro experiments demonstrated that the knockdown of ENO2 significantly increased cell apoptosis in the SW1736 and 8305C cells, coupled with a significant decrease in sphere formation.…”

Section: Discussionmentioning

confidence: 93%

“…It serves as a general marker in cell differentiation in neuroendocrine tumors and has been noted to be a well-established tumor biomarker in various types of cancers, including prostate cancer, small-cell lung cancer, and the microvascular invasion status of liver cancer ( 23 - 25 ). Several studies have suggested that ENO2 contributes to metastasis by stimulating glycolytic activity ( 26 - 28 ). The forced expression of oncogenes rescues the anoikis of mammary epithelial cells by increasing glucose utilization and decreasing oxidative stress levels ( 29 ).…”

Section: Introductionmentioning

confidence: 99%

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ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

Zhang,

Ji,

Wang

2024

Gland Surg

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Background Anoikis presents a significant barrier in the metastasis of cancer. As the most aggressive type of thyroid cancer, anaplastic thyroid cancer (ATC) exhibits a high risk of metastasis and is characterized by high mortality. Therefore, investigating the molecular mechanisms of anoikis resistance in ATC is important for devising therapeutic targets in clinical research. Methods Differentially Expressed Genes were screened in ATC cells under attached and detached culture conditions with RNA-seq. Investigate the impact of enolase 2 (ENO2) on apoptosis and spheroid formation by gain and loss of function. Changes of reactive oxygen species (ROS), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) were detected to assess redox balance. The transcriptional regulatory role of signal transducer and activator of transcription 1 (STAT1) on ENO2 was validated through Dual-Luciferase Reporter Gene Assay. Explore the impact of ENO2 expression on the formation of lung metastases in nude mice. Results We found that the glycolysis process was activated in detached ATC cells. Several genes in the glycolysis process, particularly ENO2 , a member of the enolase superfamily was upregulated in ATC cells cultured in suspension. The upregulation of ENO2 enabled the maintenance of redox balance by supplying GSH and NADPH, thereby preventing cells from undergoing anoikis. In terms of mechanism, the expression of STAT1 was enhanced in anoikis resistance cells, which in turn positively regulated the expression of ENO2. In vivo , ENO2-suppressed ATC cells resulted in a significantly lower rate of lung colonization compared to control ATC cells. Conclusions Stable expression of ENO2 and the maintenance of redox balance played a pivotal role in facilitating anoikis resistance of ATC.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

Zhang,

Ji,

Wang

2024

Gland Surg

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“…Notably, the EMT pathway, which played a pivotal role in CRC progression, was upregulated in C2, suggesting that this subtype may be highly malignant (Fig. 2 C) [ 20 , 21 ]. To identify subtypes in novel datasets, a gene classifier based on centroid was developed with reference to an article [ 16 ].We constructed a PAM classifier based on the differential genes of cell lines and apply it to the typing of TCGA cohort.…”

Section: Resultsmentioning

confidence: 99%

Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high

Cai,

Yang,

Zhang

et al. 2024

BMC Cancer

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Background Microsatellite instability-high (MSI-H) has emerged as a significant biological characteristic of colorectal cancer (CRC). Studies reported that MSI-H CRC generally had a better prognosis than microsatellite stable (MSS)/microsatellite instability-low (MSI-L) CRC, but some MSI-H CRC patients exhibited distinctive molecular characteristics and experienced a less favorable prognosis. In this study, our objective was to explore the metabolic transcript-related subtypes of MSI-H CRC and identify a biomarker for predicting survival outcomes. Methods Single-cell RNA sequencing (scRNA-seq) data of MSI-H CRC patients were obtained from the Gene Expression Omnibus (GEO) database. By utilizing the copy number variation (CNV) score, a malignant cell subpopulation was identified at the single-cell level. The metabolic landscape of various cell types was examined using metabolic pathway gene sets. Subsequently, functional experiments were conducted to investigate the biological significance of the hub gene in MSI-H CRC. Finally, the predictive potential of the hub gene was assessed using a nomogram. Results This study revealed a malignant tumor cell subpopulation from the single-cell RNA sequencing (scRNA-seq) data. MSI-H CRC was clustered into two subtypes based on the expression profiles of metabolism-related genes, and ENO2 was identified as a hub gene. Functional experiments with ENO2 knockdown and overexpression demonstrated its role in promoting CRC cell migration, invasion, glycolysis, and epithelial-mesenchymal transition (EMT) in vitro. High expression of ENO2 in MSI-H CRC patients was associated with worse clinical outcomes, including increased tumor invasion depth (p = 0.007) and greater likelihood of perineural invasion (p = 0.015). Furthermore, the nomogram and calibration curves based on ENO2 showed potential prognosis predictive performance. Conclusion Our findings suggest that ENO2 serves as a novel prognostic biomarker and is associated with the progression of MSI-H CRC.

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“…SNHG4 sponges miR‐204‐5p and promotes RCC cell proliferation and invasion 49 . The lncRNA CYTOR performs a remarkable function in promoting the development of digestive system tumors 50–52 . LINC00977 acts as an oncogene by binding STAT3 in ccRCC 53 .…”

Section: Discussionmentioning

confidence: 99%

Six‐transmembrane epithelial antigen of prostate 3 (STEAP3) is a potential prognostic biomarker in clear cell renal cell carcinoma that correlates with M2 macrophage infiltration and epithelial–mesenchymal

Wei

Zhao

et al. 2023

Cancer Reports

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BackgroundThe six‐transmembrane epithelial antigen of the prostate 3 (STEAP3) is a metalloreductase, which is essential for iron uptake. Existing literature has shown that STEAP3 may perform an important role in the onset and progression of tumors. Nonetheless, a complete pan‐cancer investigation of the prognostic significance and immune properties of STEAP3 is currently unavailable.AimsAs part of our investigation into the possible functions of STEAP3 in malignancies, we conducted a comprehensive analysis to examine the prognostic value and immune features of STEAP3 in human pan‐cancer.Methods and ResultsR and Cytoscape programs were applied to analyze and visualize the data. The expression of STEAP3 in both cell lines and tissues was measured utilizing a variety of approaches. Using the shRNA knockdown technique, we tested the viability of the A498 and 786‐O cell lines and validated their functions. Both CCK‐8 and transwell assays were conducted to estimate cell proliferation and invasion. The expression of STEAP3 was substantially elevated and was shown to be linked to prognosis in the majority of malignancies, notably in clear cell renal cell carcinoma (ccRCC). In addition, the expression of STEAP3 was shown to have a strong correlation with immune infiltrates, which in turn triggered the recruitment and polarization of M2 macrophages in ccRCC. The protein STEAP3 shows promise as a predictor of responses to immune‐checkpoint blockade (ICB) therapy. Positive links between STEAP3 and the epithelial‐mesenchymal transition (EMT), the p53 pathway, and the immune‐associated pathways were also found in the enrichment analysis. Our results illustrated that the STEAP3 expression level was substantially elevated in ccRCC tissues and suggested that it could stimulate EMT in ccRCC by downregulating CDH1.ConclusionIn a diverse range of cancers, STEAP3 might serve as a biomarker for determining the prognosis as well as a predictor of immunotherapy responsiveness. STEAP3 is a novel biological marker for determining prognosis, and it also performs a remarkable function in the promotion of tumor growth in ccRCC by enhancing invasion and EMT, as well as by triggering the recruitment and polarization of M2 macrophages.

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ENO2 Promotes Colorectal Cancer Metastasis by Interacting with the LncRNA CYTOR and Activating YAP1-Induced EMT

Cited by 24 publications

References 39 publications

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

ENO2 promotes anoikis resistance in anaplastic thyroid cancer by maintaining redox homeostasis

Investigation of ENO2 as a promising novel marker for the progression of colorectal cancer with microsatellite instability-high

Six‐transmembrane epithelial antigen of prostate 3 (STEAP3) is a potential prognostic biomarker in clear cell renal cell carcinoma that correlates with M2 macrophage infiltration and epithelial–mesenchymal

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