Overexpression of Metastasis-Associated Protein 1 is Significantly Correlated with Tumor Angiogenesis and Poor Survival in Patients with Early-Stage Non-Small Cell Lung Cancer

Li, Shuhai; Tian, Hui; Yue, Weiming; Li, Lin; Li, W.; Chen, Zhi-Tao; Hu, Wensi; Zhu, Yuyan; Qi, Lei

doi:10.1245/s10434-010-1510-5

Cited by 45 publications

(33 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the basis of the available data, it is very likely that MTA1 protein plays important and critical roles in the angiogenesis of a wide variety of human malignant tumors. The angiogenic activities of MTA1 protein in NSCLC has been reported in our previous study [31]. However, the roles of MTA1 protein in angiogenesis of NSCLC cell line have not yet been addressed.…”

Section: Discussionmentioning

confidence: 79%

Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line

Li¹,

Tian²,

Yue³

et al. 2013

ABBS

Self Cite

View full text Add to dashboard Cite

Metastasis-associated protein 1 (MTA1) high expression has been detected in a wide variety of human aggressive tumors and plays important roles in the malignant biological behaviors such as invasion, metastasis, and angiogenesis. However, the specific roles and mechanisms of MTA1 protein in regulating the malignant behaviors of non-small-cell lung cancer (NSCLC) cells still remain unclear. To elucidate the detailed functions of MTA1 protein, we down-regulated the MTA1 protein expression in NSCLC cell line by RNA interference (RNAi) in vitro, and found that down-regulation of MTA1 protein significantly inhibited the migration and invasion potentials of 95D cells. Further research revealed that down-regulation of MTA1 protein significantly decreased the activity of matrix metalloproteinase-9, which could be the mechanism responsible for the inhibition of 95D cells migration and invasion. In addition, the tube formation assay demonstrated that the number of complete tubes induced by the conditioned medium of MTA1-siRNA 95D cells was significantly smaller than that of 95D cells. These findings demonstrate that MTA1 protein plays important roles in regulating the migration, invasion, and angiogenesis potentials of 95D cells, suggesting that MTA1 protein down-regulation by RNAi might be a novel therapeutic approach to inhibit the progression of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 79%

Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line

Li¹,

Tian²,

Yue³

et al. 2013

ABBS

Self Cite

View full text Add to dashboard Cite

show abstract

“…One of the key cancer promoting activities of MTA1 is its strong association with angiogenesis in human cancer [42–46]. The underlying basis of MTA1’s role in angiogenesis includes its upregulation under hypoxic conditions in hypoxia-inducible factor-1α (HIF1α) - a key modifier of angiogenesis.…”

Section: Mta1’s Mechanism Of Action In Cancer Cellsmentioning

confidence: 99%

Role of MTA1 in cancer progression and metastasis

Sen

Gui

Kumar

2014

Cancer Metastasis Rev

View full text Add to dashboard Cite

The MTA1 protein contributes to the process of cancer progression and metastasis through multiple genes and protein targets and interacting proteins with roles in transformation, anchorage-independent growth, invasion, survival, DNA-repair, angiogenesis, hormone-independence, metastasis and therapeutic resistance. MTA proteins control a spectrum of cancer promoting processes by modulating the expression of target genes and/or the activity of MTA-interacting proteins. In the case of MTA1, these functions are manifested through post-translational modifications of MTA1 in response to upstream signals, MTA1 interaction with binding proteins and the expression of target gene products. The MTA1 coregulator interacts with nucleosomes through modified histones and is an integrator of extracellular signaling and gene activator. Studies delineating the molecular basis of dual functionality of MTA1 reveal that the functions of MTA1-chromatin modifying complexes in the context of target gene regulation are dynamic in nature. The nature and targets of MTA1-chromatin modifying complexes are also governed by the dynamic plasticity of the nucleosome landscape as well as kinetics of activation and inactivation of enzymes responsible for post-translational modifications on the MTA1 protein. These broadly applicable functions also explain why MTA1 may be a ‘hub’ gene, whose current understanding is limited to selective influences on gene with roles in cancer but further research may reveal a more global influence. Because the deregulation of enzymes and their substrates with roles in MTA1-biology is not necessarily limited to cancer, we speculate that the lessons from MTA1 as a prototype dual master coregulator will be relevant for other human diseases. In this context, the concept of the dynamic nature of corepressor versus coactivator complexes and the MTA1 proteome as a function of time to signal is likely to be generally applicable to other multi-proteins regulatory complexes in living systems.

show abstract

“…MTA1 is the founding member of the MTA family of coregulatory factors in transcriptional programs, and plays an integral role in nucleosome remodeling and histone deacetylation (NuRD) [14]. Overexpression of MTA1 is significantly associated with tumor progression and poor prognosis in NSCLC cells [15], and it has been demonstrated that the overexpression of MTA1 protein is common in early-stage NSCLC and is obviously related to tumor angiogenesis and poor survival [16]. A previous study demonstrated that MTA1 plays a key role in the regulation and mediation of the invasive phenotypes of lung cancer cells, and it has been reported that this regulation functions by altering the expression of miR [14].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Yang

Zheng

Yao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Backgrounds/Aims: MicroRNAs (miRs) often contribute to the progression of non-small cell lung cancer (NSCLC) via regulation of mRNAs that are involved in lung homeostasis. We conducted a study aimed at exploring the roles of miR-183 in the proliferation, epithelial-mesenchymal transition (EMT), invasion and migration of human NSCLC cells via targeting MTA1. Methods: NSCLC and adjacent normal tissues were collected from 194 patients with NSCLC. Positive expression of MTA1 protein was detected by immunohistochemistry. The highest levels of expression of miR-183 were detected using RT-qPCR in SPC-A-1 cells, which were selected and assigned to the following groups: blank, negative control (NC), miR-183 mimic, miR-183 inhibitor, siRNA-MTA1, and miR-183 inhibitor + siRNA-MTA1. The expression of miR-183 and the mRNA and protein expression of MTA1, E-cadherin, Vimentin, Snail, PCNA, Bax and Bcl-2 in tissues and transfected cells were measured using RT-qPCR and western blot analysis. Cell proliferation, apoptosis, migration and invasion were evaluated by CCK-8, flow cytometry, scratch tests and Transwell assays. Tumor xenografts were conducted in nude mice to determine tumor growth. Results: SPC-A-1 cells with the highest levels of miR-183 expression were selected. Compared with adjacent normal tissues, the expression of miR-183 and the mRNA and protein expression of E-cadherin and Bax were decreased in NSCLC tissues, while mRNA and protein expression of MTA1, Vimentin, snail, PCNA and Bcl-2 were increased. MiR-183 was over-expressed in the miR-183 mimic group and under-expressed in the miR-183 inhibitor and miR-183 inhibitor + siRNA-MTA1 groups. In the miR-183 mimic and siRNA-MTA1 groups, the mRNA and protein expression of E-cadherin and Bax, as well as cell apoptosis, were enhanced, while the expression levels of MTA1, Vimentin, snail, PCNA and Bcl-2 mRNA and protein, cell proliferation, migration, invasion and tumor growth were reduced relative to the blank and NC groups. The miR-183 inhibitor group exhibited an opposite trend. Conclusion: Our study indicates that miR-183 down-regulates MTA1 to inhibit the proliferation, EMT, migration and invasion of human NSCLC cells.

show abstract

Overexpression of Metastasis-Associated Protein 1 is Significantly Correlated with Tumor Angiogenesis and Poor Survival in Patients with Early-Stage Non-Small Cell Lung Cancer

Cited by 45 publications

References 46 publications

Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line

Down-regulation of MTA1 protein leads to the inhibition of migration, invasion, and angiogenesis of non-small-cell lung cancer cell line

Role of MTA1 in cancer progression and metastasis

MicroRNA-183 Acts as a Tumor Suppressor in Human Non-Small Cell Lung Cancer by Down-Regulating MTA1

Contact Info

Product

Resources

About