Metastasis-associated protein 2 (MTA2) promotes the metastasis of non-small-cell lung cancer through the inhibition of the cell adhesion molecule Ep-CAM and E-cadherin
01 Aug 2015-Japanese Journal of Clinical Oncology (Oxford University Press)-Vol. 45, Iss: 8, pp 755-766
TL;DR: Together, the experiments reveal the mechanism for metastasis-associated protein 2 in facilitating invasive potential of non-small-cell lung cancer cells, suggesting that metastatic protein 2 might be a potential therapeutic target for treating the metastasis ofnon- small- cell lung cancer.
Abstract: Objective Metastasis-associated protein 2 is considered as an intrinsic subunit of the nucleosome remodelling and histone deacetylase complex, which contributes to the epigenetic silencing genes. More and more evidence suggests that metastasis-associated protein 2 is required to maintain the malignant phenotype, but the role of metastasis-associated protein 2 function in mediating tumour metastasis in non-small-cell lung cancer has not been explored. Methods Bioinformatics was used to detect the GEO 3141 database, the online tool of Kmplot was used to confirm the high expression of metastasis-associated protein 2 in influencing 5-year overall survival. Wound-healing assay, Transwell invasion assay and Living imaging assay together showed that MTA2 shRNA inhibited cell migration and invasion in vitro and in vivo. Chromatin immunoprecipitation, quantitative chromatin immunoprecipitation and luciferase reporter assays showed metastasis-associated protein 2 binding on the promoter of the epithelial transmembrane glycoprotein (Ep-CAM) and cell adhesion molecule E-cadherin. Results The patient samples collected in our hospital show that metastasis-associated protein 2 was expressed in aggressive lung cancer cells, and its higher expression is correlated with poor prognosis. Metastasis-associated protein 2 promoted cell migration and invasion in vitro and in vivo through binding on the promoter of Ep-CAM and E-cadherin. Luciferase reporter assays showed repressed or enhanced E-cadherin or Ep-CAM promoter-driven luciferase reporter under metastasis-associated protein 2 overexpression or depletion. The changes in the level of protein and RNA implied that suppression of downstream E-cadherin or Ep-CAM was an important mechanism by which metastasis-associated protein 2 triggered epithelial-mesenchymal transition and metastasis. Conclusions Together, our experiments reveal the mechanism for metastasis-associated protein 2 in facilitating invasive potential of non-small-cell lung cancer cells, suggesting that metastasis-associated protein 2 might be a potential therapeutic target for treating the metastasis of non-small-cell lung cancer.
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TL;DR: This work analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years in order to unravel the molecular mechanism of action of both compounds.
Abstract: Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unravel the molecular mechanism of action of both compounds. Molecular targets and cellular pathways will be described. Furthermore, we also discussed the ability of these natural products act as chemopreventive and its use in association with other anticancer drugs.
94 citations
Cites background from "Metastasis-associated protein 2 (MT..."
...E-cadherin is essential for the epithelial cell behavior and evidence have shown that loss of its function is associated with the proliferation of a number of cancers, including lung [191], pancreatic [192], oral [193], liver [194], gastric [195], prostate [196] and ovarian [197]....
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TL;DR: Through literature research, it is found that silencing of SNHGs through small interfering RNAs or short hairpin RNAs is very effective in both in vitro and in vivo experiments by lowering the aggressiveness of solid cancers.
Abstract: The small nucleolar RNA host genes (SNHGs) are a group of long non-coding RNAs, which are reported in many studies as being overexpressed in various cancers. With very few exceptions, the SNHGs (SNHG1, SNHG3, SNHG5, SNHG6, SNHG7, SNHG12, SNHG15, SNHG16, SNHG20) are recognized as inducing increased proliferation, cell cycle progression, invasion, and metastasis of cancer cells, which makes this class of transcripts a viable biomarker for cancer development and aggressiveness. Through our literature research, we also found that silencing of SNHGs through small interfering RNAs or short hairpin RNAs is very effective in both in vitro and in vivo experiments by lowering the aggressiveness of solid cancers. The knockdown of SNHG as a new cancer therapeutic option should be investigated more in the future.
77 citations
TL;DR: Investigation of free-floating tumor cell clusters in surgically resected lung cancer specimens and their possible relation to gross examination procedures found 93% of the loose tissue fragments could be explained by mechanical forces associated with tissue handling.
Abstract: The World Health Organization Classification of Lung Tumors considers "Spread Through Air Spaces" a form of invasion in lung adenocarcinoma. The recently described spread of free-floating cell clusters during lung specimen sectioning, otherwise known as "Spread Through A Knife Surface," represents an ex vivo artifact. The purpose of this study was to prospectively investigate the presence and frequency of these free-floating tumor cell clusters in surgically resected lung cancer specimens and their possible relation to gross examination procedures. A prospective, multi-institutional study of non-small cell lung cancer resection specimen was undertaken. At prosection the first cut was made with a clean knife; the second cut was made in a parallel plane to the first. Four tissue blocks were taken from upper and lower parts of first and second cuts. Hematoxylin and eosin-stained slides were examined for displaced benign and/or malignant tissue fragments. Forty-four resection specimens were studied. The mean number of tumor clusters for blocks 1 to 4 was 0.36, 1.44, 1.86, and 1.95, respectively, and for benign fragments was 0.11, 0.11, 0.13, and 0.25, respectively. Almost all cell clusters were intra-alveolar. Comparison of tumor cell clusters in block 1 with blocks 2 to 4 was significant with P-values (Friedman test for repeated measures 0.03) 0.031, 0.02, and 0.05, respectively. Overall 93% of the loose tissue fragments could be explained by mechanical forces associated with tissue handling. While the 2015 World Health Organization Classification of Lung Tumors recognizes Spread Through Air Spaces as a form of lung cancer invasion, such is debatable and in many instances likely represents mechanical artifact, including dissemination along the prosecting knife blade.
76 citations
TL;DR: The structure, expression and functions of the MTA family of genes in the context of cancer cells, including 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.
54 citations
TL;DR: The results suggest that miR-1236-3p functions as a tumor suppressor in GC and could be a promising therapeutic target for GC.
Abstract: MicroRNAs deregulation are common in human tumor progression. miR-1236-3p has been reported to function as tumor suppressor microRNA in various malignancies. The aim of this study was to demonstrate the downregulated expression of miR-1236-3p in gastric cancer (GC) tissues and cell lines, and clarify its biological function in GC. Real-time polymerase chain reaction was used to measure the mRNA level of miR-1236-3p in GC. Dual luciferase assay was used to demonstrate that MTA2 was one of the candidate target genes of miR-1236-3p. Western blots were utilized to detect the protein levels. Cell function assays were also performed to determine the function of miR-1236-3p in GC. miR-1236-3p expression, which was associated with lymph node metastasis, differentiation and clinical stage, was significantly reduced in GC tissues and cell lines. miR-1236-3p over-expression could inhibit GC cell proliferation, migration and invasion, and inhibition of miR-1236-3p expression had opposite effects. Furthermore, we demonstrated that MTA2 was a candidate target of miR-1236-3p, and miR-1236-3p over-expression significantly inhibited the process of epithelial–mesenchymal transition. We also found that miR-1236-3p could suppress the PI3K/Akt signaling pathway in GC cells. Our results suggest that miR-1236-3p functions as a tumor suppressor in GC and could be a promising therapeutic target for GC.
40 citations
Cites background from "Metastasis-associated protein 2 (MT..."
...MTA2 is a member of the metastasis-associated gene family that has been reported to be closely associated with tumor progression [25]....
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...Among the candidates, MTA2, a potent oncogene that is frequently upregulated in human cancers [25, 26], was predicted to be a miR-1236-3p target by all three of the algorithms and was selected for further experimental verification....
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