Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

Brüning, Ansgar; Blankenstein, Thomas; Jückstöck, Julia; Mylonas, Ioannis

doi:10.1007/s10555-014-9520-6

Cited by 13 publications

(14 citation statements)

References 96 publications

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“…MTA-1 was discovered in 1993, demonstrating high expression levels with high metastatic potential in rat breast cancer cells ( 26 ). Subsequently, it was confirmed that MTA-1 is involved in the invasion and metastasis of tumors, and is involved in regulating a variety of other malignant tumor processes, including cell proliferation, angiogenesis and resistance to chemotherapy ( 26 – 30 ). Furthermore, MTA-1 is associated with high recurrence and a poor prognosis, and eventually causes cancer.…”

Section: Discussionmentioning

confidence: 99%

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

Wang

2016

Molecular Medicine Reports

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The aim of the present study was to evaluate the association between Period2 (Per2) and the occurrence and development of ovarian cancer, in addition to evaluating the effect of this gene on the growth and metastasis of ovarian cancer in nude mice xenograft models. The detection of Per2 by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting methods at various stages of ovarian cancer in tumor tissue samples was conducted. Nude mice xenograft models of ovarian cancer were constructed using an ovarian cancer cell line and, using a gene transfection technique, exogenous infusion of the recombinant gene, Per2, was performed. To assess for the successful and stable expression of Per2 in the tumor tissue, levels of Per2 expression in the nude mice xenograft models were detected by RT-qPCR. During the experimental period, the tumor volumes were measured every three days. Two weeks following treatment cessation, the nude mice were sacrificed and the tumor weight and volume were measured. Furthermore, detection of the changes in expression levels of metastasis-associated gene 1 (MTA-1) and tumor metastasis suppressor gene, non-metastasis protein 23-H1 (nm23-H1), and the expression change of autophagy-associated signal transduction pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) kinase were analyzed. The findings demonstrated that with ovarian cancer stage development, the expression of Per2 gradually reduced or ceased. In addition, exogenous Per2 was successfully and stably expressed in nude mice tumor tissue samples. Furthermore, in the Per2 overexpression group, MTA-1 protein expression was significantly reduced when compared with the phosphate-buffered saline (PBS) control and empty plasmid groups, while nm23-H1 protein expression was significantly higher when compared with those two groups. The expression levels of PI3K and PKB kinase, which are marker proteins of the autophagy associated signaling pathway PI3K/PKB, were significantly downregulated, when compared with the PBS control and empty plasmid groups (P<0.001). Thus, it was demonstrated that Per2 is closely associated with the development of ovarian cancer, and late-stage ovarian cancer is associated with Per2 mutation or deletion. Per2 overexpression, via exogenous infusion reduced the ovarian cancer growth rate, which was demonstrated by a significant increase in the tumor inhibition rate. In addition, Per2 may inhibit the expression of MTA-1 and promote the expression of nm23-H1 to restrict ovarian tumor growth and metastasis. Finally, it is hypothesized that Per2 affects autophagy by interfering with the PI3K/PKB signaling pathway, causing inhibition of tumor angiogenesis in order to inhibit tumor growth.

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Section: Discussionmentioning

confidence: 99%

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

Wang

2016

Molecular Medicine Reports

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“…MTA1 is involved in the positive regulation of protein autoubiquitination. In fact, this gene has been characterized as an important oncogene facilitating cervical cancer progression and metastasis [ 16 , 17 ]. Knockdown of MTA1 partly restores p53 and E-cadherin expression in cervical cancer cells and subsequently decreases their invasion, migration, and adhesion capabilities [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Preserved miR-361-3p Expression Is an Independent Prognostic Indicator of Favorable Survival in Cervical Cancer

et al. 2018

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In this study, we aimed to assess the independent prognostic value of miR-361-3p in terms of overall survival (OS) and recurrence-free survival (RFS) in cervical cancer, as well as its possible regulative network. A retrospective analysis was performed by using data from the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC). Results showed that decreased miR-361-3p expression was associated with lymphovascular invasion and poor responses to primary therapy. The patients with recurrence and the deceased cases had substantially lower miR-361-3p expression compared to their respective controls. By generating Kaplan-Meier curves of OS and RFS, we found that high miR-361-3p expression was associated with better survival outcome. More importantly, univariate and multivariate analysis confirmed that high miR-361-3p expression was an independent indicator of favorable OS (HR: 0.377, 95% CI: 0.233–0.608, p < 0.001) and RFS (HR: 0.398, 95% CI: 0.192–0.825, p = 0.013). By performing bioinformatic analysis, we identified 24 genes that were negatively correlated with miR-361-3p expression. Among the potential targeting genes, SOST, MTA1, TFRC, and YAP1 are involved in some important signaling pathways modulating cervical cancer cell invasion, migration, and drug sensitivity. Therefore, it is meaningful to verify the potential regulative effect of miR-361-3p on the expression of these genes in the future.

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“…However, information about the impact of MTA alterations on the survival rates of cancer patients is only available for a few cancer-types such as hepatocellular carcinomas wherein MTA1 overexpression has been shown to be associated with a poorer survival (reviewed by Toh and Nicholson, 2014). While MTA3 may be either downregulated in cancer such as in breast cancer and endometrioid adenocarcinomas (Brüning, A. et al, 2014) or upregulated in human cancer such as in non-small cell lung cancer (Li et al, 2013b), human placenta and chorionic carcinoma cells (Brüning, A. et al, 2009). The nature of relationship between the status of MTA3 and survival of cancer patients is somewhat not fully examined at the moment.…”

Section: Cellular Functions Of Mta Familymentioning

confidence: 99%

Structure, expression and functions of MTA genes

Kumar

Wang

2016

Gene

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Metastatic associated proteins (MTA) are integrators of upstream regulatory signals with the ability to act as master coregulators for modifying gene transcriptional activity. The MTA family includes three genes and multiple alternatively spliced variants. The MTA proteins neither have their own enzymatic activity nor have been shown to directly interact with DNA. However, MTA proteins interact with a variety of chromatin remodeling factors and complexes with enzymatic activities for modulating the plasticity of nucleosomes, leading to the repression or derepression of target genes or other extra-nuclear and nucleosome remodeling and histone deacetylase (NuRD)-complex independent activities. The functions of MTA family members are driven by the steady state levels and subcellular localization of MTA proteins, the dynamic nature of modifying signals and enzymes, the structural features and post-translational modification of protein domains, interactions with binding proteins, and the nature of the engaged and resulting features of nucleosomes in the proximity of target genes. In general, MTA1 and MTA2 are the most upregulated genes in human cancer and correlate well with aggressive phenotypes, therapeutic resistance, poor prognosis and ultimately, unfavorable survival of cancer patients. Here we will discuss the structure, expression and functions of the MTA family of genes in the context of cancer cells.

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Function and regulation of MTA1 and MTA3 in malignancies of the female reproductive system

Cited by 13 publications

References 96 publications

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

Effects of Per2 overexpression on growth inhibition and metastasis, and on MTA1, nm23-H1 and the autophagy-associated PI3K/PKB signaling pathway in nude mice xenograft models of ovarian cancer

Preserved miR-361-3p Expression Is an Independent Prognostic Indicator of Favorable Survival in Cervical Cancer

Structure, expression and functions of MTA genes

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