&amp;alpha;‑enolase is highly expressed in liver cancer and promotes cancer cell invasion and metastasis

Zhang, Lihong; Lu, Tao; Yang, Ye; Hu, Liangfeng

doi:10.3892/ol.2020.12003

Cited by 7 publications

(7 citation statements)

References 24 publications

(23 reference statements)

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“…Proteins linked to pyruvate metabolic processes (Aldoc, Eno1, Gpi, Me2, Pck1, and Pck2) are also of interest. For instance, Eno1 is an important biomarker of carcinogenicity and is highly expressed in liver cancer . A proteomic investigation into pulmonary injuries in mice induced by microcystin-LR found Eno1 increase in abundance and contributed to protein phosphorylation and energy metabolism, which are defense-related mechanisms connected to PP2A inhibition caused by microcystin-LR .…”

Section: Discussionsupporting

confidence: 54%

“…For instance, Eno1 is an important biomarker of carcinogenicity and is highly expressed in liver cancer. 47 A proteomic investigation into pulmonary injuries in mice induced by microcystin-LR found Eno1 increase in abundance and contributed to protein phosphorylation and energy metabolism, which are defense-related mechanisms connected to PP2A inhibition caused by microcystin-LR. 48 For the present study, GO bioinformatics in the liver also indicates clusters of significantly dysregulated proteins may be connected to regulatory pathways responsible for cell replication (Dock8, Dpp3, Gbf1, Icmt, Mgat1, and Serpina10), cytoskeletal structure (Dctn3, Dnah8, and Spire1), stress responses (Aldoc, Eno1, Ethe1, Gpi, Mgat1, Me2, Nt5c3b, Pck1, Pck2, Ugdh, and Uprt), and DNA repair (Irx1, Myt1l, Vgll2, Zc3h4, Zc3h6, and Znf729).…”

Section: Toxicity In Fish Tissues Go Enrichment Analysis Inmentioning

confidence: 99%

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Cyanotoxins within and Outside of Microcystis aeruginosa Cause Adverse Effects in Rainbow Trout (Oncorhynchus mykiss)

Shahmohamadloo

Almirall

Simmons

et al. 2021

Environ. Sci. Technol.

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The global expansion of toxic Microcystis blooms, and production of cyanotoxins including microcystins, are an increasing risk to freshwater fish. Differentiating intracellular and extracellular microcystin toxicity pathways (i.e., within and outside of cyanobacterial cells) in fish is necessary to assess the severity of risks to populations that encounter harmful algal blooms in pre-to-postsenescent stages. To address this, adult and juvenile Rainbow Trout (Oncorhynchus mykiss) were, respectively, exposed for 96 h to intracellular and extracellular microcystins (0, 20, and 100 μg L–1) produced by Microcystis aeruginosa. Fish were dissected at 24 h intervals for histopathology, targeted microcystin quantification, and nontargeted proteomics. Rainbow Trout accumulated intracellular and extracellular microcystins in all tissues within 24 h, with greater accumulation in the extracellular state. Proteomics revealed intracellular and extracellular microcystins caused sublethal toxicity by significantly dysregulating proteins linked to the cytoskeletal structure, stress responses, and DNA repair in all tissues. Pyruvate metabolism in livers, anion binding in kidneys, and myopathy in muscles were also significantly impacted. Histopathology corroborated these findings with evidence of necrosis, apoptosis, and hemorrhage at similar severity in both microcystin treatments. We demonstrate that sublethal concentrations of intracellular and extracellular microcystins cause adverse effects in Rainbow Trout after short-term exposure.

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Section: Discussionsupporting

confidence: 54%

Section: Toxicity In Fish Tissues Go Enrichment Analysis Inmentioning

confidence: 99%

Cyanotoxins within and Outside of Microcystis aeruginosa Cause Adverse Effects in Rainbow Trout (Oncorhynchus mykiss)

Shahmohamadloo

Almirall

Simmons

et al. 2021

Environ. Sci. Technol.

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“…Alpha-enolase is overexpressed in multiple human cancer types, contributing to increased glycolysis and tumor growth ( Altenberg and Greulich, 2004 ; Chang et al, 2006 ; He et al, 2007 ; Tsai et al, 2010 ; Capello et al, 2011 ; Song et al, 2014 ; Fu et al, 2015 ; Sun et al, 2017 , 2019 ; Zhan et al, 2017 ; Yin et al, 2018 ; Zhang et al, 2018 , 2020 ; Cheng et al, 2019 ; Ji et al, 2019 ; Qiao et al, 2019 ; Xu et al, 2019 ; Chen et al, 2020 ). ENO1 overexpression is often associated with anti-ENO1 autoantibody responses and may have prognostic and diagnostic value in certain cancers ( Table 1 ; Adamus et al, 1998 ; Tomaino et al, 2011 ; Pranay et al, 2013 ; Hsiao et al, 2015 ; Griggio et al, 2017 ; Zhang et al, 2020 ). ENO1 is also localized on the surface of cancer cells where it enhances plasmin formation ( Miles et al, 1991 ; Redlitz et al, 1995 ) to promote extracellular matrix degradation, cell migration, invasion, and metastasis ( Hsiao et al, 2013 ; Didiasova et al, 2014 ; Principe et al, 2015 , 2017 ; Zakrzewicz et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Alpha-Enolase: Emerging Tumor-Associated Antigen, Cancer Biomarker, and Oncotherapeutic Target

et al. 2021

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Alpha-enolase, also known as enolase-1 (ENO1), is a glycolytic enzyme that “moonlights” as a plasminogen receptor in the cell surface, particularly in tumors, contributing to cancer cell proliferation, migration, invasion, and metastasis. ENO1 also promotes other oncogenic events, including protein-protein interactions that regulate glycolysis, activation of signaling pathways, and resistance to chemotherapy. ENO1 overexpression has been established in a broad range of human cancers and is often associated with poor prognosis. This increased expression is usually accompanied by the generation of anti-ENO1 autoantibodies in some cancer patients, making this protein a tumor associated antigen. These autoantibodies are common in patients with cancer associated retinopathy, where they exert pathogenic effects, and may be triggered by immunodominant peptides within the ENO1 sequence or by posttranslational modifications. ENO1 overexpression in multiple cancer types, localization in the tumor cell surface, and demonstrated targetability make this protein a promising cancer biomarker and therapeutic target. This mini-review summarizes our current knowledge of ENO1 functions in cancer and its growing potential as a cancer biomarker and guide for the development of novel anti-tumor treatments.

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“…A study by TAKASHIMA [30] con rmed that high expression of ENO1 was closely associated with tumor size and tumor recurrence in hepatocellular carcinoma, and our experiments veri ed this conclusion from ENO1 serum levels. In addition, previous studies have shown that high expression of ENO1 promotes tumor cell proliferation and invasion, accelerates tumor metastasis, and inhibits tumor cell apoptosis [7][8][9][10][11] . This suggests that the ndings of ENO1 at the cellular level are consistent with those at the serum level.…”

Section: Discussionmentioning

confidence: 99%

“…If Αenolase is located in the nucleus, its encoded protein can in uence tumourigenesis and development through transcriptional repression [10] . Studies have shown that ENO1 is aberrantly highly expressed in a variety of tumor cells, and that its high expression promotes proliferation, invasion and suppresses apoptosis [11] . In many tumors, ENO1 or anti-ENO1 antibodies have the potential to function as tumor markers.…”

Section: Introductionmentioning

confidence: 99%

Study on The Expression and Correlation of Alpha-Enolase (Eno1) in The Serum of Patients With Hepatocellular Carcinoma

Luo¹,

Ma²,

Liu³

et al. 2021

Preprint

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Background: Serum tumor markers for the early detection of hepatocellular carcinoma is limited. This study analyzed the distribution and differences of ENO1 in the serum of healthy people, patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma. Furthermore, the distribution and correlation of ENO1 in the clinical data of patients with hepatocellular carcinoma were explored and its clinical diagnostic effect as well as combined diagnostic effect with AFP were compared. In addition, the effect of ENO1 on the survival of patients with hepatocellular carcinoma were also evaluated. The study will provide data basis for the application of ENO1 in the diagnosis of hepatocellular carcinoma, and provide new ideas for the study of molecular markers and therapeutic targets for hepatocellular carcinoma.Methods: In accordance with the inclusion and exclusion criteria, Patients diagnosed at the Infectious Diseases Department of the General Hospital of Ningxia Medical University and the healthy check-up population at the medical check-up centre from May 2012 to March 2017 were screened for inclusion in the study. T The final study subjects were 181, 28 patients with chronic hepatitis B (CHB), 31 patients with liver cirrhosis (LC), 104 patients with liver cancer (HCC) and 18 healthy people (NC). Clinical data and sera were collected from all study subjects, tissue specimens were collected from some patients. The levels of serum ENO1 and AFP were measured by ELISA. QRT-PCR and Western Blot t were used to detect the relative expression of ENO1 mRNA and protein in liver cancer tissues and paracancerous tissues. Statistical analysis was performed by t-test, bivariate Spearman correlation test, curve regression analysis, ROC curve analysis and survival curve analysis.Results: The relative expression of ENO1 mRNA and protein was significantly upregulated in hepatocellular carcinoma tissues relative to paraneoplastic tissues (p<0.05), ENO1 levels in the serum of HCC patients were sequentially higher than those of CHB patients, LC patients and healthy subjects, with significant differences (p<0.05). The differences in the distribution of serum ENO1 levels in the clinical data subgroups alpha fetoprotein (AFP) status, TNM stage (II vs III, III vs IV) were not statistically significant (p>0.05), there were statistically significant differences (p<0.05) in the distribution of gender, tumor size, whether the tumor was metastatic or not, TNM stage (I vs II) and Edmondson's grading in the clinical information subgroup. The difference in the distribution among clinical information subgroups of whether the tumor had recurred was highly significant (p < 0.01). Serum ENO1 levels showed a significant positive correlation with AFP levels (Spearman's correlation coefficient 0.312, p=0.001**), the diagnostic sensitivity and specificity of ENO1 in this group of HCC patients were 0.673 and 0.831 (AUC=0.782, cutoff=75.96, p=0.0001), respectively, the sensitivity of ENO1 in conjunction with AFP in the diagnosis of HCC in this group was 0.740 and the specificity was 0.723 (AUC=0.835, p=0.0001), the AUCs of ENO1 in the diagnosis of HCC tumor size, whether the tumor was metastatic, TNM I stage, Edmondson classification and whether the tumor recurred in this group were 0.663 (0.546-0.781, P=0.012*), 0.681 (0.574-0.787, P=0.002**), 0.553 (0.421-0.686, P=0.386), 0.710 (0.602-0.819, P=0.001**), and 0.685 (0.580-0.789, P=0.001**).Conclusion: Serum ENO1 levels were significantly correlated with the occurrence, progression and metastasis of hepatocellular carcinoma, staging and postoperative survival of patients. ENO1 may be a candidate diagnostic marker for early diagnosis and evaluation of hepatocellular carcinoma progression, and can be used in combination with AFP as an auxiliary diagnostic function.

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α‑enolase is highly expressed in liver cancer and promotes cancer cell invasion and metastasis

Cited by 7 publications

References 24 publications

Cyanotoxins within and Outside of Microcystis aeruginosa Cause Adverse Effects in Rainbow Trout (Oncorhynchus mykiss)

Cyanotoxins within and Outside of Microcystis aeruginosa Cause Adverse Effects in Rainbow Trout (Oncorhynchus mykiss)

Alpha-Enolase: Emerging Tumor-Associated Antigen, Cancer Biomarker, and Oncotherapeutic Target

Study on The Expression and Correlation of Alpha-Enolase (Eno1) in The Serum of Patients With Hepatocellular Carcinoma

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