Kinesin Family member 4A: A Potential Predictor for Progression of Human Oral Cancer
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{"title"=>"Kinesin family member 4A: A potential predictor for progression of human oral cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Yasuyuki", "last_name"=>"Minakawa", "scopus_author_id"=>"55203470800"}, {"first_name"=>"Atsushi", "last_name"=>"Kasamatsu", "scopus_author_id"=>"8557672100"}, {"first_name"=>"Hirofumi", "last_name"=>"Koike", "scopus_author_id"=>"8565366000"}, {"first_name"=>"Morihiro", "last_name"=>"Higo", "scopus_author_id"=>"9236962600"}, {"first_name"=>"Dai", "last_name"=>"Nakashima", "scopus_author_id"=>"8565365900"}, {"first_name"=>"Yukinao", "last_name"=>"Kouzu", "scopus_author_id"=>"8724561200"}, {"first_name"=>"Yosuke", "last_name"=>"Sakamoto", "scopus_author_id"=>"26642753800"}, {"first_name"=>"Katsunori", "last_name"=>"Ogawara", "scopus_author_id"=>"9236958000"}, {"first_name"=>"Masashi", "last_name"=>"Shiiba", "scopus_author_id"=>"7004277975"}, {"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"=>{"sgr"=>"84893579853", "pmid"=>"24386490", "pui"=>"372325123", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84893579853", "doi"=>"10.1371/journal.pone.0085951", "issn"=>"19326203"}, "id"=>"03d68a79-e427-3815-bc1c-2eb0da5549ce", "abstract"=>"BACKGROUND: Kinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC.\\n\\nMETHODS: The KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to in vitro data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated.\\n\\nRESULTS: KIF4A mRNA and protein were up-regulated significantly (P < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (P < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (P < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (P < 0.05) with tumoral size.\\n\\nCONCLUSIONS: Our results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs.", "link"=>"http://www.mendeley.com/research/kinesin-family-member-4a-potential-predictor-progression-human-oral-cancer", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>4, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>6, "Student > Postgraduate"=>3, "Student > Master"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>5, "Neuroscience"=>1, "Physics and Astronomy"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1331946"], "description"=>"<p>(<b>A</b>) Quantification of KIF4A mRNA expression in OSCC-derived cellular lines by qRT-PCR analysis. Significant up-regulation of KIF4A mRNA is seen in seven OSCC-derived cellular lines compared with the HNOKs (<i>P</i> < 0.05, Mann-Whitney U test). Data are expressed as the means ± SEM of triplicate results. (<b>B</b>) Immunoblotting analysis of KIF4A protein in the OSCC-derived cellular lines and HNOKs. KIF4A protein expression is up-regulated in the OSCC-derived cellular lines compared with that in the HNOKs. Densitometric KIF4A protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of the HNOKs (<i>P</i> < 0.05, Mann-Whitney U test).</p>", "links"=>[], "tags"=>["kif4a", "oscc-derived", "cellular"], "article_id"=>888936, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_KIF4A_expression_in_OSCC_derived_cellular_lines_/888936", "title"=>"Evaluation of KIF4A expression in OSCC-derived cellular lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331948"], "description"=>"<p>(<b>A</b>) qRT-PCR shows that KIF4A mRNA expression in the shKIF4A cells (HSC-3-and Ca9-22-derived transfectants; 2 clones each) is significantly lower than in the shMock cells (<i>P</i> < 0.05, Mann-Whitney U test). (<b>B</b>) Immunoblotting analysis shows that the KIF4A protein levels in shKIF4A-transfected cells (HSC-3- and Ca9-22-derived transfectants; 2 clones each) also have decreased markedly compared with that in the shMock cells (<i>P</i> < 0.05, Mann-Whitney U test).</p>", "links"=>[], "tags"=>["kif4a", "shkif4a"], "article_id"=>888938, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_KIF4A_in_shKIF4A_cells_/888938", "title"=>"Expression of KIF4A in shKIF4A cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331950"], "description"=>"<p>Localization of BUB1 and MAD2 to the kinetochores is compared in shKIF4A and shMock cells by immunofluorescence. (<b>A</b>) BUB1 on kinetochores increased in shKIF4A cells compared with that in the shMock cells (green, KIF4A; red, BUB1; blue, DNA). (<b>B</b>) Appropriate localization of MAD2 is seen in shKIF4A cells, whereas kinetochore localization is not seen in the shMock cells (green, KIF4A; red, MAD2; blue, DNA).</p>", "links"=>[], "tags"=>["bub1", "mad2", "prometaphase", "shmock", "shkif4a"], "article_id"=>888940, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Localization_of_BUB1_and_MAD2_during_the_prometaphase_in_shMock_and_shKIF4A_cells_/888940", "title"=>"Localization of BUB1 and MAD2 during the prometaphase in shMock and shKIF4A cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331952"], "description"=>"<p>To investigate SAC activation and cell-cycle progression, we determined the expression levels of CDC20 and cyclin B1, and DNA content in the G0-G1, S, and, G2-M phases. (<b>A</b>) shKIF4A cells showed down-regulation of CDC20 and up-regulation of cyclin B1 (HSC-3- and Ca9-22-derived transfectants; 2 clones each) compared with shMock cells (<i>P</i> < 0.05, Mann-Whitney U test). (<b>B</b>) Flow cytometric analysis was performed to investigate the cell cycle in shKIF4A and shMock cells. The percentage of the G2/M phase in shKIF4A cells (HSC-3- and Ca9-22-derived transfectants; 2 clones each) has increased markedly compared with shMock cells (<i>P</i> < 0.05, Mann-Whitney’s U test).</p>", "links"=>[], "tags"=>["sac"], "article_id"=>888942, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_shKIF4A_promote_G2_M_arrest_via_SAC_activation_/888942", "title"=>"shKIF4A promote G2/M arrest via SAC activation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331953"], "description"=>"<p>To determine the effect of shKIF4A on cellular proliferation, shKIF4A and shMock cells were seeded in six-well plates at a density of 1×10<sup>4</sup> viable cells/well. Both transfectants were counted on seven consecutive days. The cellular growth of shKIF4A-transfected cells (HSC-3- and Cas9-22-derived transfectants; 2 clones each) were significantly inhibited compared with shMock cells after 7 days (168 hours). The results were expressed as the means ± SEM of values from three assays. The asterisks indicate significant differences between the shKIF4A and shMock cells (<i>P</i> < 0.05, Mann-Whitney U test).</p>", "links"=>[], "tags"=>["cellular", "shkif4a"], "article_id"=>888943, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduced_cellular_growth_in_shKIF4A_cells_/888943", "title"=>"Reduced cellular growth in shKIF4A cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331955"], "description"=>"<p>Representative IHC results for KIF4A protein in normal oral tissue (<b>A</b>) and primary OSCC (<b>B</b>). <b>A</b>, <b>B</b>: Original magnification, ×400. Scale bars, 10 μm. Strong KIF4A immunoreactivity was detected in primary OSCCs; normal oral tissues show almost negative immunostaining. <b>C</b>: The state of KIF4A protein expression in primary OSCCs (n=106) and the normal counterparts. The KIF4A IHC scores were calculated as follows: IHC score = 0× (number of unstained cells in the field) +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 KIF4A IHC scores for normal oral tissues and OSCCs ranged from 26.5 to 103 (median, 66.5) and 62.3 to 188 (median, 131), respectively. KIF4A protein expression levels in OSCCs are significantly (<i>P</i> < 0.05, Mann-Whitney’s U test) higher than in normal oral tissues.</p>", "links"=>[], "tags"=>["kif4a"], "article_id"=>888945, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Evaluation_of_KIF4A_protein_expression_in_primary_OSCCs_/888945", "title"=>"Evaluation of KIF4A protein expression in primary OSCCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1331957"], "description"=>"<div><p>Background</p><p>Kinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC.</p> <p>Methods</p><p>The KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to <i>in</i><i>vitro</i> data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated. </p> <p>Results</p><p>KIF4A mRNA and protein were up-regulated significantly (<i>P</i> < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (<i>P</i> < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (<i>P</i> < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (<i>P</i> < 0.05) with tumoral size. </p> <p>Conclusions</p><p>Our results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs.</p> </div>", "links"=>[], "tags"=>["predictor", "progression"], "article_id"=>888947, "categories"=>["Biological Sciences"], "users"=>["Yasuyuki Minakawa", "Atsushi Kasamatsu", "Hirofumi Koike", "Morihiro Higo", "Dai Nakashima", "Yukinao Kouzu", "Yosuke Sakamoto", "Katsunori Ogawara", "Masashi Shiiba", "Hideki Tanzawa", "Katsuhiro Uzawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0085951"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinesin_Family_member_4A_A_Potential_Predictor_for_Progression_of_Human_Oral_Cancer_/888947", "title"=>"Kinesin Family member 4A: A Potential Predictor for Progression of Human Oral Cancer", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-12-30 03:03:43"}

PMC Usage Stats | Further Information

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Relative Metric

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