Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells
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{"title"=>"Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Hongyan", "last_name"=>"Wang", "scopus_author_id"=>"36457307600"}, {"first_name"=>"Liangsheng", "last_name"=>"Fan", "scopus_author_id"=>"35190275800"}, {"first_name"=>"Juncheng", "last_name"=>"Wei", "scopus_author_id"=>"13806888200"}, {"first_name"=>"Yanjie", "last_name"=>"Weng", "scopus_author_id"=>"24475840900"}, {"first_name"=>"Li", "last_name"=>"Zhou", "scopus_author_id"=>"57199017397"}, {"first_name"=>"Ying", "last_name"=>"Shi", "scopus_author_id"=>"56183674000"}, {"first_name"=>"Wenjuan", "last_name"=>"Zhou", "scopus_author_id"=>"55475952300"}, {"first_name"=>"Ding", "last_name"=>"Ma", "scopus_author_id"=>"26643491700"}, {"first_name"=>"Changyu", "last_name"=>"Wang", "scopus_author_id"=>"56072873500"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)", "sgr"=>"84870828422", "pui"=>"366234526", "pmid"=>"23227138", "issn"=>"19326203", "scopus"=>"2-s2.0-84870828422", "doi"=>"10.1371/journal.pone.0046888"}, "id"=>"eb040e05-da51-3097-b1c5-86587a3f03c1", "abstract"=>"Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis.", "link"=>"http://www.mendeley.com/research/akt-mediates-metastasisassociated-gene-1-mta1-regulating-expression-ecadherin-promoting-invasiveness", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>2, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Materials Science"=>1, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>6, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Russia"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/530404"], "description"=>"<p>(A) Western blotting results demonstrated that treatment with MTA1 siRNA increased E-cadherin expression after 48 hours. An asterisk (*) or diamond (◊) indicates a statistically significant difference (p<0.05) in the MTA1 or E-cadherin levels, respectively, compared with the negative-control siRNA-transfected cells. (B) A Western blotting analysis also demonstrated that transient transfection with a plasmid that encoded full-length MTA1 decreased E-cadherin expression after 48 hours. An asterisk (*) or diamond (◊) indicates a statistically significant difference (p<0.05) in the MTA1 or E-cadherin levels, respectively, compared with the cells transfected with an empty vector. The changes were quantified (top). All of the experiments were repeated three times.</p>", "links"=>[], "tags"=>["regulates", "E-cadherin"], "article_id"=>200898, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046888.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MTA1_regulates_E_cadherin_expression_/200898", "title"=>"MTA1 regulates E-cadherin expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-05 00:14:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/530156"], "description"=>"<p>(A–C) Typical results for the MTA1 staining pattern determined by immunohistochemistry are shown in normal prostate tissue (A), localized prostate cancer tissue (B), and metastatic prostate cancer tissue (C). The results in B and C showed MTA1 expression in both nuclei and cytoplasm. The original magnification for A–C is 200 fold and detailed with enlarged view is 400 fold. (D) A quantitative RT-PCR analysis of the MTA1 RNA levels in 2B4 and 1E8 cells (top). An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the 2B4 cells. (E) The protein expression levels of MTA1 in 2B4 and 1E8 cells were analyzed by Western blotting using specific antibodies, and the results were quantified (top). An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the 2B4 cells. The experiments were repeated three times.</p>", "links"=>[], "tags"=>["mta1", "prostate", "cancer"], "article_id"=>200645, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046888.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_expression_of_MTA1_in_prostate_cancer_tissue_and_prostate_cancer_cells_/200645", "title"=>"The expression of MTA1 in prostate cancer tissue and prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-05 00:10:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/285452", "https://ndownloader.figshare.com/files/285529", "https://ndownloader.figshare.com/files/285577", "https://ndownloader.figshare.com/files/285613", "https://ndownloader.figshare.com/files/285641"], "description"=>"<div><p>Human metastasis-associated gene 1 (MTA1) is highly associated with the metastasis of prostate cancer; however, the molecular functions of MTA1 that facilitate metastasis remain unclear. In this study, we demonstrate that the silencing of MTA1 by siRNA treatment results in the upregulation of E-cadherin expression by the phosphorylation of AKT (p-AKT) and decreases the invasiveness of prostate cancer cells. We show that MTA1 is expressed in over 90% of prostate cancer tissues, especially metastatic prostate cancer tissue, comparing to non-expression in normal prostate tissue. RT-PCR analysis and Western blot assay showed that MTA1 expression is significantly higher in highly metastatic prostate cancer PC-3M-1E8 cells (1E8) than in poorly metastatic prostate cancer PC-3M-2B4 cells (2B4). Silencing MTA1 expression by siRNA treatment in 1E8 cells increased the cellular malignant characters, including the cellular adhesive ability, decreased the cellular invasive ability and changed the polarity of cellular cytoskeleton. 1E8 cells over-expressing MTA1 had a reduced expression of E-cadherin, while 1E8 cells treated with MTA1 siRNA had a higher expression of E-cadherin. The expression of phosphorylated AKT (p-AKT) or the inhibition of p-AKT by wortmannin treatment (100 nM) significantly altered the function of MTA1 in the regulation of E-cadherin expression. Alterations in E-cadherin expression changed the role of p-AKT in cellular malignant characters. All of these results demonstrate that MTA1 plays an important role in controlling the malignant transformation of prostate cancer cells through the p-AKT/E-cadherin pathway. This study also provides a new mechanistic role for MTA1 in the regulation of prostate cancer metastasis.</p> </div>", "links"=>[], "tags"=>["akt", "mediates", "metastasis-associated", "regulating", "E-cadherin", "promoting", "invasiveness", "prostate", "cancer", "cells"], "article_id"=>116262, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0046888.s001", "https://dx.doi.org/10.1371/journal.pone.0046888.s002", "https://dx.doi.org/10.1371/journal.pone.0046888.s003", "https://dx.doi.org/10.1371/journal.pone.0046888.s004", "https://dx.doi.org/10.1371/journal.pone.0046888.s005"], "stats"=>{"downloads"=>5, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Akt_Mediates_Metastasis_Associated_Gene_1_MTA1_Regulating_the_Expression_of_E_cadherin_and_Promoting_the_Invasiveness_of_Prostate_Cancer_Cells__/116262", "title"=>"Akt Mediates Metastasis-Associated Gene 1 (MTA1) Regulating the Expression of E-cadherin and Promoting the Invasiveness of Prostate Cancer Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-12-05 01:44:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/530631"], "description"=>"<p>(A) The cells were treated with the myr-AKT plasmid or empty vector for 48 hours in the presence or absence of E-cadherin siRNA. The adhesive ability was tested using the MTT assay, and a typical experimental result is shown. An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the cells transfected with an empty vector. A triangle (Δ) indicates a statistically significant difference (p<0.05) compared to the cells transfected with the myr-AKT-encoding plasmid in the absence of E-cadherin siRNA. (B) The cells were incubated with wortmannin (100 nM) or DMSO for 24 hours and then treated with or without E-cadherin siRNA for 48 hours. Using the MTT assay, the adhesive ability of the cells was tested. An asterisk (*) indicates a statistically significant difference (p<0.05) compared with DMSO-treated cells. A triangle (Δ) indicates a statistically significant difference (p<0.05) compared with the wortmannin-treated cells in the absence of E-cadherin siRNA. (C, D, and E) The cells were treated with the myr-AKT plasmid or an empty vector for 48 hours in the presence or absence of the E-cadherin plasmid. A Matrigel<sup>TM</sup>-coated transwell system was used to analyze the invasive capabilities of the cells. The quantification of the number of invasive cells from the bottom of the transwell inserts is shown (right panel). An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the cells transfected with an empty vector. A triangle (Δ) indicates a statistically significant difference (p<0.05) compared with the cells transfected with a myr-AKT-encoding plasmid in the absence of E-cadherin siRNA. (F, G, and H) The cells were treated with the myr-AKT plasmid or an empty vector for 48 hours in the presence or absence of the E-cadherin plasmid. The changes in the cellular cytoskeleton were monitored by confocal microscopy. Red staining represents α-tubulin, and blue staining represents the nuclei (400 fold). (I, J, and K) The cells were treated with wortmannin (100 nM) or DMSO for 24 hours and then treated with or without E-cadherin siRNA for 48 hours. A Matrigel<sup>TM</sup>-coated transwell system was used to measure changes in the cellular invasive ability. The quantification of the number of invasive cells from the bottom of the transwell insert is shown (right panel). An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the DMSO-treated cells. A triangle (Δ) indicates a statistically significant difference (p<0.05) compared with the wortmannin-treated cells in the absence of E-cadherin siRNA. (L, M, and N) The cells were treated with wortmannin (100 nM) or DMSO for 24 hours and then treated with or without E-cadherin siRNA for 48 hours. The changes in the cellular cytoskeleton were monitored by confocal microscopy. Red staining represents α-tubulin, and blue staining represents the nuclei (400 fold). A representative result from three experiments is shown for all data.</p>", "links"=>[], "tags"=>["forced", "over-expression", "E-cadherin", "changes", "p-akt", "mediated", "malignant"], "article_id"=>201115, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046888.g005", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_forced_over_expression_or_silencing_of_E_cadherin_changes_the_p_AKT_mediated_malignant_phenotypes_/201115", "title"=>"The forced over-expression or silencing of E-cadherin changes the p-AKT mediated malignant phenotypes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-05 00:18:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/530514"], "description"=>"<p>(A) A Western blotting analysis showed that treatment with MTA1 siRNA could inhibit AKT phosphorylation after a 48 hours siRNA treatment. An asterisk (*) and diamond (◊) indicates a statistically significant difference (p<0.05) in the MTA1 and E-cadherin levels, respectively, compared with the negative-control siRNA-transfected cells. (B) The cells were incubated with either the p-AKT inhibitor wortmannin (100 nM) or DMSO for various times from 24 hours to 48 hours, and the cellular proteins were extracted. A Western blotting analysis showed that wortmannin treatment promoted the expression of E-cadherin and inhibited the expression of MTA1 after 24 hours. An asterisk (*), diamond (◊), or triangle (Δ) indicates a statistically significant difference (p<0.05) in the MTA1, E-cadherin or p-AKT levels, respectively, compared with the DMSO-treated cells. (C) The forced over expression of p-AKT by transient transfection of the myr-AKT plasmid decreased the expression of E-cadherin and increased the expression of MTA1 after 24 hours. The quantification of the bands is shown (top). (D) The cells were transfected with MTA1 siRNA in the presence or absence of the myr-AKT plasmid or wortmannin for 48 hours. A Western blotting analysis was used to evaluate the changes in E-cadherin expression. An asterisk (*), diamond (◊), or triangle (Δ) indicates a statistically significant difference (p<0.05) in the MTA1, E-cadherin or p-AKT levels, respectively, compared with the negative-control siRNA-transfected cells. The quantification of the bands intensities is shown (top). All experiments were repeated three times.</p>", "links"=>[], "tags"=>["regulates", "E-cadherin", "phosphorylation", "activation", "akt"], "article_id"=>201005, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046888.g004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MTA1_regulates_E_cadherin_through_the_phosphorylation_and_activation_of_AKT_p_AKT_/201005", "title"=>"MTA1 regulates E-cadherin through the phosphorylation and activation of AKT (p-AKT).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-05 00:16:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/530303"], "description"=>"<p>(A) Treatment with MTA1 siRNA decreased MTA1 expression efficiently and enhanced E-cadherin expression. The protein levels were analyzed using Western blotting and were normalized to β-actin. The quantification of the band intensities is shown (top). An asterisk (*) or diamond (◊) indicates a statistically significant difference (p<0.05) in the MTA1 or E-cadherin levels, respectively, compared with the nontreated cells and the negative-control siRNA-transfected cells, n = 3. (B) The adhesive rate was quantified by the MTT assay, and a representative experiment is shown. The ability of the cells to adhere to a solid surface was significantly upregulated in the cells that had been treated with MTA1 siRNA. An asterisk (*) indicates a statistically significant difference (p<0.05) compared to the nontreated cells and negative-control siRNA-transfected cells. (C, D, and E) Using a Matrigel<sup>TM</sup>-coated transwell system, the invasive ability of the cells treated MTA1 siRNA was tested. The quantification of the number of invasive cells from the bottom of the transwell inserts is shown in the lower panel. An asterisk (*) indicates a statistically significant difference (p<0.05) compared with the nontreated cells and negative-control siRNA-transfected cells. (F, G, and H) The changes in the cytoskeleton structure were detected by confocal microscopy: Red staining represents α-tubulin. Blue staining represents the nuclei. The ‘feet’ were shortened, and the polarization was weakened in cells treated with MTA1 siRNA. These changes indicate a reduced ability to move (400 fold). A representative result from three independent experiments is shown for all data.</p>", "links"=>[], "tags"=>["mta1", "malignant", "phenotypes", "1e8"], "article_id"=>200789, "categories"=>["Cancer", "Genetics"], "users"=>["Hongyan Wang", "Liangsheng Fan", "Juncheng Wei", "Yanjie Weng", "Li Zhou", "Ying Shi", "Wenjuan Zhou", "Ding Ma", "Changyu Wang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0046888.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_influence_of_MTA1_expression_on_the_malignant_phenotypes_of_1E8_cells_/200789", "title"=>"The influence of MTA1 expression on the malignant phenotypes of 1E8 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-05 00:13:09"}

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Relative Metric

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