Current Molecular and Genetic Aspects of Pancreatic Cancer, the Role of Metastasis Associated Proteins (MTA): A Review

Pavlidis, Efstathios T; Pavlidis, Theodosios

doi:10.1080/08941939.2016.1269854

Cited by 10 publications

(8 citation statements)

References 117 publications

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“…These results suggest that these peptides could have broader applicability. Several authors have reported that MTA1 is expressed at low levels in most normal cells [7, 10, 15], and accordingly, we did not detect significant lysis activity by peptide-induced CTLs toward the normal cells HUVEC and Het-1A, perhaps because of the weak MTA1 expression in these cells. Although MTA1-specific T cells can lyse MTA1 + tumor cells rather than normal cells, which express low levels of MTA1, and the body weight of mice in the peptide or protein group was not affected.…”

Section: Discussioncontrasting

confidence: 57%

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HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response

Zhai

Zhou

et al. 2018

Journal of Immunology Research

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Overexpression of metastasis-associated protein 1 (MTA1) has been observed in many human malignancies and is significantly related to tumor invasion and metastasis, therapeutic resistance to radiation and chemotherapy, making MTA1 an ideal candidate tumor antigen. We identified several human leukocyte antigen- (HLA-) A2-restricted epitopes in MTA1 and evaluated their binding ability to HLA-A∗0201 molecules. Subsequently, a recombinant fragment encompassing the dominant epitopes, MTA1(1–283), was expressed, and the abilities of the selected epitopes of MTA1 and the MTA1(1–283) fragment to induce cytotoxic T lymphocytes (CTLs) were examined. Our results indicated that the epitopes and MTA1(1–283) fragment elicited HLA-A2-restricted and antigen-specific CTL responses both in vitro and in vivo. The new epitopes identified here may help promote the development of new therapeutic vaccines for HLA-A2+ patients expressing MTA1.

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Section: Discussioncontrasting

confidence: 57%

“…Our previous study found that MTA1 was upregulated in tumor cells treated with chemotherapy drugs such as cisplatin, 5-fluorouracil, and pacitaxel. Therefore, MTA1 has been considered an ideal target for cancer immunotherapy [15]. However, the immune-dominant CTL epitopes of MTA1 have not been identified.…”

Section: Introductionmentioning

confidence: 99%

HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response

Zhai

Zhou

et al. 2018

Journal of Immunology Research

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“…Studies have reported the upregulation of MTA2 in many types of cancers, such as gastric cancer 14, 15, breast cancer 11, and non-small-cell lung carcinoma (NSCLC) 16. MTA2 was observed to be highly expressed in pancreatic ductal adenocarcinoma (PDAC) and correlated with aggressive properties and poor prognosis 17.…”

Section: Discussionmentioning

confidence: 99%

Metastasis-associated protein 2 regulates human hepatocellular carcinoma metastasis progression through modulating p38MAPK/MMP2 pathways

Hsu¹,

Chiou²,

Lin³

et al. 2019

J. Cancer

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Studies have shown the overexpression of metastasis-associated protein 2 (MTA2) to be associated with hepatocellular carcinoma (HCC) progression. However, the molecular mechanism of MTA2 expression in HCC is unclear. In our study, we found a higher level of MTA2 in HCC tissues than in normal tissues and a significant correlation between tumor grade and overall survival of HCC patients. We also found that MTA2 inhibition reduced the migration and invasion capabilities of HCC cells, independent of cell proliferation. Mechanistic studies have suggested that MTA2 protein and mRNA are more highly expressed in SK-Hep-1 and Huh-7 cells compared with other HCC cells. MTA2 silencing drastically reduced migration and invasion capability and also inhibited matrix metalloproteinase 2 (MMP2) at the transcriptional and translation levels in both cells. In addition, treatment with the MMP2 antibody markedly impaired MTA2-knockdown-mediated inhibition of migration and invasion in SK-Hep-1 cells. Furthermore, MTA2 knockdown reduced the phosphorylation of the p38MAPK protein, whereas the inhibition of p38MAPK (SB203580 or si-p38) confirmed that blocking the p38MAPK pathway mediated MTA2-knockdown-inhibited migration and invasion in SK-Hep-1 cells. We demonstrated the molecular mechanism by which MTA2 inhibits human HCC cell metastasis through the p38MAPK/MMP2 pathways, which might be helpful in determining the diagnostic value of this protein in patients with HCC

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“…It has been established that there are significant differences between Asian and Caucasian populations in genetic and epigenetic background, dietary, environmental factors (114, 115). These factors are essential for not only initiation and progression, but also metastasis of cancers (116, 117). Mutations and extensive polymorphisms of SIRT1 were found in Chinese and Japanese (118–121) and 41 cancer lines (122).…”

Section: Discussionmentioning

confidence: 99%

Survival and Clinicopathological Significance of SIRT1 Expression in Cancers: A Meta-Analysis

Sun

Zhang

et al. 2019

Front. Endocrinol.

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Background: Silent information regulator 2 homolog 1 (SIRT1) is an evolutionarily conserved enzymes with nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase activity. SIRT1 is involved in a large variety of cellular processes, such as genomic stability, energy metabolism, senescence, gene transcription, and oxidative stress. SIRT1 has long been recognized as both a tumor promoter and tumor suppressor. Its prognostic role in cancers remains controversial.Methods: A meta-analysis of 13,138 subjects in 63 articles from PubMed, EMBASE, and Cochrane Library was performed to evaluate survival and clinicopathological significance of SIRT1 expression in various cancers.Results: The pooled results of meta-analysis showed that elevated expression of SIRT1 implies a poor overall survival (OS) of cancer patients [Hazard Ratio (HR) = 1.566, 95% CI: 1.293–1.895, P < 0.0001], disease free survival (DFS) (HR = 1.631, 95% CI: 1.250–2.130, P = 0.0003), event free survival (EFS) (HR = 2.534, 95% CI: 1.602–4.009, P = 0.0001), and progress-free survival (PFS) (HR = 3.325 95% CI: 2.762–4.003, P < 0.0001). Elevated SIRT1 level was associated with tumor stage [Relative Risk (RR) = 1.299, 95% CI: 1.114–1.514, P = 0.0008], lymph node metastasis (RR = 1.172, 95% CI: 1.010–1.360, P = 0.0363), and distant metastasis (RR = 1.562, 95% CI: 1.022–2.387, P = 0.0392). Meta-regression and subgroup analysis revealed that ethnic background has influence on the role of SIRT1 expression in predicting survival and clinicopathological characteristics of cancers. Overexpression of SIRT1 predicted a worse OS and higher TNM stage and lymphatic metastasis in Asian population especially in China.Conclusion: Our data suggested that elevated expression of SIRT1 predicted a poor OS, DFS, EFS, PFS, but not for recurrence-free survival (RFS) and cancer-specific survival (CCS). SIRT1 overexpression was associated with higher tumor stage, lymph node metastasis, and distant metastasis. SIRT1-mediated molecular events and biological processes could be an underlying mechanism for metastasis and SIRT1 is a therapeutic target for inhibiting metastasis, leading to good prognosis.

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Current Molecular and Genetic Aspects of Pancreatic Cancer, the Role of Metastasis Associated Proteins (MTA): A Review

Abstract: Carcinogenesis and implicated oncogenes, either activators or repressors, concentrate much research interest, as well as being useful as biomarkers and for targeted therapy. MTA proteins could become useful diagnostic and prognostic biomarkers in current management of pancreatic cancer.

Cited by 10 publications

References 117 publications

HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response

HLA-A2-Restricted Epitopes Identified from MTA1 Could Elicit Antigen-Specific Cytotoxic T Lymphocyte Response

Metastasis-associated protein 2 regulates human hepatocellular carcinoma metastasis progression through modulating p38MAPK/MMP2 pathways

Survival and Clinicopathological Significance of SIRT1 Expression in Cancers: A Meta-Analysis

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