Overexpression of LIM and SH3 Protein 1 Leading to Accelerated G2/M Phase Transition Contributes to Enhanced Tumourigenesis in Oral Cancer
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{"title"=>"Overexpression of LIM and SH3 protein 1 leading to accelerated G2/M phase transition contributes to enhanced tumourigenesis in oral cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Fumie", "last_name"=>"Shimizu", "scopus_author_id"=>"55978212700"}, {"first_name"=>"Masashi", "last_name"=>"Shiiba", "scopus_author_id"=>"7004277975"}, {"first_name"=>"Katsunori", "last_name"=>"Ogawara", "scopus_author_id"=>"9236958000"}, {"first_name"=>"Ryota", "last_name"=>"Kimura", "scopus_author_id"=>"55933323800"}, {"first_name"=>"Yasuyuki", "last_name"=>"Minakawa", "scopus_author_id"=>"55203470800"}, {"first_name"=>"Takao", "last_name"=>"Baba", "scopus_author_id"=>"55457325500"}, {"first_name"=>"Satoshi", "last_name"=>"Yokota", "scopus_author_id"=>"55114941100"}, {"first_name"=>"Dai", "last_name"=>"Nakashima", "scopus_author_id"=>"8565365900"}, {"first_name"=>"Morihiro", "last_name"=>"Higo", "scopus_author_id"=>"9236962600"}, {"first_name"=>"Atsushi", "last_name"=>"Kasamatsu", "scopus_author_id"=>"8557672100"}, {"first_name"=>"Yosuke", "last_name"=>"Sakamoto", "scopus_author_id"=>"26642753800"}, {"first_name"=>"Hideki", "last_name"=>"Tanzawa", "scopus_author_id"=>"7006934032"}, {"first_name"=>"Katsuhiro", "last_name"=>"Uzawa", "scopus_author_id"=>"35478592900"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"24386158", "doi"=>"10.1371/journal.pone.0083187", "pui"=>"372005917", "issn"=>"19326203", "sgr"=>"84891294738", "scopus"=>"2-s2.0-84891294738"}, "id"=>"5a4a9fbc-9748-322f-922e-2dee85a58f3b", "abstract"=>"BACKGROUND: LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein involved in several malignant tumors. However, its role in oral squamous cell carcinoma (OSCC) is unknown. The aim of this study was to characterize the role and molecular status/mechanism of LASP-1 in OSCC. METHODS: We evaluated LASP-1 mRNA and protein expressions in OSCC-derived cell lines and primary OSCCs. Using an shRNA system, we analyzed the effect of LASP-1 on the biology and function of the OSCC cell lines, HSC-3 and Ca9-22. The cells also were subcutaneously injected to evaluate tumor growth in vivo. Data were analyzed by the Fisher's exact test or the Mann-Whitney U test. Bonferroni correction was used for multiple testing. RESULTS: Significant up-regulation of LASP-1 was detected in OSCC-derived cell lines (n = 7, P<0.007) and primary OSCCs (n = 50, P<0.001) compared to normal controls. LASP-1 knockdown cells significantly inhibited cellular proliferation compared with shMock-transfected cells (P<0.025) by arresting cell-cycle progression at the G2 phase. We observed dramatic reduction in the growth of shLASP-1 OSCC xenografts compared with shMock xenografts in vivo. CONCLUSION: Our results suggested that overexpression of LASP-1 is linked closely to oral tumourigenicity and further provide novel evidence that LASP-1 plays an essential role in tumor cellular growth by mediating G2/M transition.", "link"=>"http://www.mendeley.com/research/overexpression-lim-sh3-protein-1-leading-accelerated-g2m-phase-transition-contributes-enhanced-tumou", "reader_count"=>12, "reader_count_by_academic_status"=>{"Librarian"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Researcher"=>1, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>1, "Other"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>7, "Agricultural and Biological Sciences"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Unspecified"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1329088"], "description"=>"<p>(A) Quantification of <i>LASP-1</i> mRNA expression in OSCC-derived cell lines by qRT-PCR analysis. mRNA expression levels are normalized to GAPDH. Significant up-regulation of <i>LASP-1</i> mRNA is seen in seven OSCC-derived cell lines compared with that in HNOKs. Data are expressed as the means ± SEM of triplicate results (*<i>P</i><0.007; Mann-Whitney U test with Bonferroni correction). (B) Immunoblotting analysis of LASP-1 protein in the OSCC-derived cell lines and HNOKs. LASP-1 protein expression is up-regulated in the OSCC-derived cell lines compared with that in the HNOKs. Densitometric LASP-1 protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of the HNOKs.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "lasp-1", "oscc-derived"], "article_id"=>886990, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_LASP_1_expression_in_OSCC_derived_cell_lines_/886990", "title"=>"Evaluation of LASP-1 expression in OSCC-derived cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329090"], "description"=>"<p>(A) The status of LASP-1 protein expression in primary OSCCs (n = 50) and the normal counterparts based on an IHC scoring system. IHC scores are calculated as follows: IHC score = 1×(number of weakly stained cells in the field)+2×(number of moderately stained cells in the field)+3×(number of intensely stained cells in the field). The LASP-1 IHC scores for normal oral tissues and OSCCs range from 2.5 to 97 (median, 35) and 43 to 265 (median, 178), respectively. LASP-1 protein expression levels in OSCCs are significantly higher than in normal oral tissues (*<i>P</i><0.001; Mann-Whitney U test). (B, C) Representative IHC results of LASP-1 in normal oral tissues and primary OSCCs. Original magnification, ×100. Scale bars, 5 µm. LASP-1 is highly overexpressed in OSCCs compared to normal oral tissues.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "lasp-1"], "article_id"=>886992, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_LASP_1_protein_expression_in_primary_OSCCs_/886992", "title"=>"Evaluation of LASP-1 protein expression in primary OSCCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329091"], "description"=>"<p>(A) Expression of <i>LASP-1 </i>mRNA in shMock- and shLASP-1-transfected cells (HSC-3- and Ca9-22-derived transfectants; 2 clones each). The <i>LASP-1</i> mRNA expression in the shLASP-1 is significantly (*<i>P</i><0.025; Mann-Whitney U test with Bonferroni correction) lower than that in the shMock-transfected cells. (B) Immunoblotting analysis of LASP-1 protein in the shMock- and shLASP-1-transfected cells (HSC-3- and Ca9-22-derived transfectants; 2 clones each). The LASP-1 protein in the shLASP-1 transfected cells is depleted markedly compared with the shMock-transfected cells.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "lasp-1", "shlasp-1-transfected"], "article_id"=>886993, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_LASP_1_in_shLASP_1_transfected_cells_/886993", "title"=>"Expression of LASP-1 in shLASP-1-transfected cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329093"], "description"=>"<p>To determine the effect of shLASP-1 on cellular proliferation, shLASP-1- and shMock-transfected cells were seeded in six-well plates at a density of 1×10<sup>4</sup> viable cells/well. The shLASP-1 transfected HSC-3 and Ca9-22 cells have a significant (*<i>P</i><0.025; Mann-Whitney U test with Bonferroni correction) decrease in cellular growth compared with the shMock-transfected cells.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "shlasp-1-transfected"], "article_id"=>886995, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proliferation_of_shLASP_1_transfected_cells_/886995", "title"=>"Proliferation of shLASP-1-transfected cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329094"], "description"=>"<p>(A) Flow cytometric determination of DNA content was analyzed using the Accuri C6 Flow Cytometer. shLASP-1-transfected HSC-3 and Ca9-22 cells show significant (*<i>P</i><0.025; Mann-Whitney U test with Bonferroni correction) G2 phase accumulation as opposed to the shMock-transfected cells. (B) Immunoblotting analysis shows down-regulation of cyclin A and cyclin B and up-regulation of phospho-cdc2 in the knockdown cells.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "g2"], "article_id"=>886996, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_shLASP_1_promotes_G2_arrest_/886996", "title"=>"shLASP-1 promotes G2 arrest.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329098"], "description"=>"<p>shLASP-1- and shMock-transfected cells (HSC-3 and Ca9-22) were injected subcutaneously into the backs of female nude mice (n = 3). The tumor growth of the shLASP-1-injected mice is significantly (*<i>P</i><0.05; Mann-Whitney U test) inhibited compared to the shMock-injected mice. Immunohistochemistry clearly demonstrated decreased immunostaining for LASP-1 in the shLASP-1-derived tumors than shMock injected mice. H&E staining confirmed the presence of tumor cells. Original magnification, ×200.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers"], "article_id"=>887000, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LASP_1_promotes_tumor_growth_in_vivo_/887000", "title"=>"LASP-1 promotes tumor growth <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329099"], "description"=>"<p>P<0.05.</p>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "clinicopathological", "patients", "oscc", "lasp-1"], "article_id"=>887001, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlations_between_clinicopathological_characteristics_of_patients_with_OSCC_and_LASP_1_protein_expression_levels_/887001", "title"=>"Correlations between clinicopathological characteristics of patients with OSCC and LASP-1 protein expression levels.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-12-26 04:20:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1329101", "https://ndownloader.figshare.com/files/1329102"], "description"=>"<div><p>Background</p><p>LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein involved in several malignant tumors. However, its role in oral squamous cell carcinoma (OSCC) is unknown. The aim of this study was to characterize the role and molecular status/mechanism of LASP-1 in OSCC.</p><p>Methods</p><p>We evaluated <i>LASP-1</i> mRNA and protein expressions in OSCC-derived cell lines and primary OSCCs. Using an shRNA system, we analyzed the effect of LASP-1 on the biology and function of the OSCC cell lines, HSC-3 and Ca9-22. The cells also were subcutaneously injected to evaluate tumor growth <i>in vivo</i>. Data were analyzed by the Fisher’s exact test or the Mann-Whitney U test. Bonferroni correction was used for multiple testing.</p><p>Results</p><p>Significant up-regulation of LASP-1 was detected in OSCC-derived cell lines (n = 7, <i>P</i><0.007) and primary OSCCs (n = 50, <i>P</i><0.001) compared to normal controls. LASP-1 knockdown cells significantly inhibited cellular proliferation compared with shMock-transfected cells (<i>P</i><0.025) by arresting cell-cycle progression at the G2 phase. We observed dramatic reduction in the growth of shLASP-1 OSCC xenografts compared with shMock xenografts <i>in vivo</i>.</p><p>Conclusion</p><p>Our results suggested that overexpression of LASP-1 is linked closely to oral tumourigenicity and further provide novel evidence that LASP-1 plays an essential role in tumor cellular growth by mediating G2/M transition.</p></div>", "links"=>[], "tags"=>["genetics", "Cancer genetics", "Molecular cell biology", "cell adhesion", "gene expression", "oncology", "Basic cancer research", "Tumor physiology", "Cancer risk factors", "Genetic causes of cancer", "Cancers and neoplasms", "Skin tumors", "Oral mucosal cancers", "otorhinolaryngology", "Head and neck cancers", "lim", "sh3", "accelerated", "contributes", "enhanced", "tumourigenesis"], "article_id"=>887003, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Fumie Shimizu", "Masashi Shiiba", "Katsunori Ogawara", "Ryota Kimura", "Yasuyuki Minakawa", "Takao Baba", "Satoshi Yokota", "Dai Nakashima", "Morihiro Higo", "Atsushi Kasamatsu", "Yosuke Sakamoto", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0083187.s001", "https://dx.doi.org/10.1371/journal.pone.0083187.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overexpression_of_LIM_and_SH3_Protein_1_Leading_to_Accelerated_G2_M_Phase_Transition_Contributes_to_Enhanced_Tumourigenesis_in_Oral_Cancer_/887003", "title"=>"Overexpression of LIM and SH3 Protein 1 Leading to Accelerated G2/M Phase Transition Contributes to Enhanced Tumourigenesis in Oral Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-12-26 04:20:36"}

PMC Usage Stats | Further Information

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Relative Metric

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