ABL Tyrosine Kinase Inhibition Variable Effects on the Invasive Properties of Different Triple Negative Breast Cancer Cell Lines
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{"title"=>"ABL tyrosine kinase inhibition variable effects on the invasive properties of different triple negative breast cancer cell lines", "type"=>"journal", "authors"=>[{"first_name"=>"Clément", "last_name"=>"Chevalier", "scopus_author_id"=>"56574811500"}, {"first_name"=>"Aude", "last_name"=>"Cannet", "scopus_author_id"=>"56455219300"}, {"first_name"=>"Simon", "last_name"=>"Descamps", "scopus_author_id"=>"6603389510"}, {"first_name"=>"Audrey", "last_name"=>"Sirvent", "scopus_author_id"=>"8740624700"}, {"first_name"=>"Valérie", "last_name"=>"Simon", "scopus_author_id"=>"7103308306"}, {"first_name"=>"Serge", "last_name"=>"Roche", "scopus_author_id"=>"7005127029"}, {"first_name"=>"Christine", "last_name"=>"Benistant", "scopus_author_id"=>"6701767955"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"603281627", "sgr"=>"84925862490", "doi"=>"10.1371/journal.pone.0118854", "scopus"=>"2-s2.0-84925862490", "pmid"=>"25803821"}, "id"=>"b84d8e4e-8cc4-315e-865d-12f0cdae4649", "abstract"=>"The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN) breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity in vitro. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of ABL expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.", "link"=>"http://www.mendeley.com/research/abl-tyrosine-kinase-inhibition-variable-effects-invasive-properties-different-triple-negative-breast", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Master"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Materials Science"=>1, "Agricultural and Biological Sciences"=>6, "Medicine and Dentistry"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Belgium"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1984417"], "description"=>"<p><b>(A, B)</b> BT-549 cells were infected with retroviruses expressing control (ShCtl) or anti-<i>TRIO</i> shRNAs (ShTrio1 and ShTrio2) and then plated on Oregon Green 488 gelatin. After fixation, actin cytoskeleton morphology and gelatin degradation by cells were analyzed as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118854#pone.0118854.g001\" target=\"_blank\">Fig. 1A</a>. <b>(C)</b> TRIO expression in lysates from BT-549 cells infected with control shRNA, ShTrio1 or ShTrio2. Densitometry quantification normalized to ponceau is shown. <b>(D, E and F)</b> Actin cytoskeleton morphology and gelatin degradation by MDA-MB 231 cells infected with control shRNA, ShTrio1 or ShTrio2. <b>(G)</b> BT-549 cells were transfected with plasmids encoding mCherry-Trio or the GEF domain 1 (D1) of TRIO (mCherry-GEFD1). After 48h cells were plated on Oregon Green 488 gelatin and incubated with 100nM nilotinib. <b>(H)</b> The degradation area in transfected BT-549 cells was quantified as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118854#pone.0118854.g001\" target=\"_blank\">Fig. 1B</a>. *p<0.05. Scale bar: 20μm.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352548, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g007", "stats"=>{"downloads"=>2, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Involvement_of_the_TRIO_RAC1_axis_downstream_of_the_ABL_kinases_in_the_regulation_of_invadopodia_/1352548", "title"=>"Involvement of the TRIO/RAC1 axis downstream of the ABL kinases in the regulation of invadopodia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984387"], "description"=>"<p><b>(A)</b> BT-549 and MDA-MB 231 cells were seeded on Oregon Green 488 gelatin-coated coverslips and treated with DMSO, 5μM SU6656, 5μM imatinib, (10–100) nM nilotinib or 100nM dasatinib for 3h and then fixed for immunofluorescence studies. The actin cytoskeleton morphology was visualized by labeling F-actin with Alexa 598-conjugated phalloidin and the cell degradation activity was assessed based on the appearance of black spots, due to gelatin degradation, in the green fluorescent background of the gelatin matrix. Scale bar: 20μm. <b>(B)</b> Quantification of the matrix degradation area per cell (in μm<sup>2</sup>; mean ± SEM of more than 100 cells/condition from three different experiments). *p<0.05. <b>(C)</b> BT-549 and MDA-MB 231 cells were seeded on Oregon Green 488 gelatin-coated coverslips and treated with DMSO or two different concentrations of nilotinib (10nM and 100nM) for 3h and then fixed for immunofluorescence analysis to quantify the degradation area per cell (in μm<sup>2</sup>; mean ± SEM). *p<0.05 <b>(D)</b> BT-549 cells were transfected twice at an interval of 24h control siRNA (Ctrl) or <i>ABL</i> siRNA. After 48h, cells were plated on Oregon Green 488 gelatin-coated coverslips for 3h. After fixation, the degradation area per cell (in μm<sup>2</sup>; mean ± SEM) was quantified. *p<0.05, NS: non-significant. <b>(E)</b> BT-549 and MDA-MB 231 cells transfected twice with control (Ctrl) or <i>ABL</i> siRNAs as in (D) were lysed and immunoprecipitated with an anti-ABL antibody. Densitometry quantification normalized to tubulin is shown.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352524, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g001", "stats"=>{"downloads"=>2, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Variable_outcomes_of_ABL_kinase_inhibition_on_the_invasive_properties_of_TN_breast_cancer_cells_/1352524", "title"=>"Variable outcomes of ABL kinase inhibition on the invasive properties of TN breast cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984392"], "description"=>"<p><b>(A, B)</b> BT-549 cells and MDA—MB 231 were seeded in the Matrigel-coated upper compartment of Boyden chambers and incubated with DMSO or 100nM nilotinib for 24h before fixation. Cell nuclei in the lower chamber were stained with Hoechst (representative images in left panels, scale bar: 500μm. Insets show higher magnification of the boxed region) to quantify in whole well the number of cells that migrated from the top chamber through the Matrigel-coated filter pores. Shown is the cell invasion (mean ± SD, n = 3 experiments, right panels) relative to control (DMSO); *p<0.05 compared to control cells. <b>(C)</b> Cells were seeded in the upper compartment of Boyden chambers and incubated with DMSO or 100nM nilotinib for 45 min; quantification (mean ± SD, n = 3) of cells that migrated through the uncoated filter was as in (A); *p<0.05, NS: non-significant compared to DMSO treated cells.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352529, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nilotinib_effect_on_cancer_cell_invasion_and_migration_/1352529", "title"=>"Nilotinib effect on cancer cell invasion and migration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984431", "https://ndownloader.figshare.com/files/1984432", "https://ndownloader.figshare.com/files/1984433", "https://ndownloader.figshare.com/files/1984434"], "description"=>"<div><p>The non-receptor tyrosine kinase ABL drives myeloid progenitor expansion in human chronic myeloid leukemia. ABL inhibition by the tyrosine kinase inhibitor nilotinib is a first-line treatment for this disease. Recently, ABL has also been implicated in the transforming properties of solid tumors, including triple negative (TN) breast cancer. TN breast cancers are highly metastatic and several cell lines derived from these tumors display high invasive activity <i>in vitro</i>. This feature is associated with the activation of actin-rich membrane structures called invadopodia that promote extracellular matrix degradation. Here, we investigated nilotinib effect on the invasive and migratory properties of different TN breast cancer cell lines. Nilotinib decreased both matrix degradation and invasion in the TN breast cancer cell lines MDA-MB 231 and MDA-MB 468. However, and unexpectedly, nilotinib increased by two-fold the invasive properties of the TN breast cancer cell line BT-549 and of Src-transformed fibroblasts. Both display much higher levels of ABL kinase activity compared to MDA-MB 231. Similar effects were obtained by siRNA-mediated down-regulation of <i>ABL</i> expression, confirming ABL central role in this process. ABL anti-tumor effect in BT-549 cells and Src-transformed fibroblasts was not dependent on EGF secretion, as recently reported in neck and squamous carcinoma cells. Rather, we identified the TRIO-RAC1 axis as an important downstream element of ABL activity in these cancer cells. In conclusion, the observation that TN breast cancer cell lines respond differently to ABL inhibitors could have implications for future therapies.</p></div>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352562, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0118854.s001", "https://dx.doi.org/10.1371/journal.pone.0118854.s002", "https://dx.doi.org/10.1371/journal.pone.0118854.s003", "https://dx.doi.org/10.1371/journal.pone.0118854.s004"], "stats"=>{"downloads"=>5, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ABL_Tyrosine_Kinase_Inhibition_Variable_Effects_on_the_Invasive_Properties_of_Different_Triple_Negative_Breast_Cancer_Cell_Lines_/1352562", "title"=>"ABL Tyrosine Kinase Inhibition Variable Effects on the Invasive Properties of Different Triple Negative Breast Cancer Cell Lines", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984395"], "description"=>"<p><b>(A, B)</b> BT-549 cells and MDA—MB 231 were transfected twice with control (Ctrl) and Abl siRNAs and were seeded in the Matrigel-coated upper compartment of Boyden chambers and incubated for 24h before fixation. Cell nuclei in the lower chamber were stained with Hoechst (representative images in left panels. Scale bar: 250μm) to quantify in whole well the number of cells that migrated from the top chamber through the Matrigel-coated filter pores. Shown is the cell invasion (mean ± SD, n = 3 experiments, right panels) relative to ctrl siRNA; *p<0.05 compared to control cells. <b>(C)</b> Ctrl and Abl siRNA transfected cells were seeded in the upper compartment of Boyden chambers and incubated for 45 min. Quantification (mean ± SD, n = 3) of cells that migrated through the uncoated filter was as in (A); *p<0.05, NS: non-significant compared to Ctrl siRNA.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352532, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Abl_downregulation_effect_on_cancer_cell_invasion_and_migration_/1352532", "title"=>"Abl downregulation effect on cancer cell invasion and migration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984397"], "description"=>"<p><b>(A)</b> Triton X-100 lysates of BT-549 and MDA-MB 231 cells incubated with DMSO (-) or 100nM nilotinib (+) were used for <i>in vitro</i> kinase assays to test ABL kinase activity. Immunoprecipitates were incubated with GST-Crk as a substrate and P<sup>32</sup>-labeled ATP. P<sup>32</sup> incorporation by GST-Crk was detected by autoradiography. The Abl content of immunoprecipitates and densitometry quantification normalized to Abl are also shown. <b>(B)</b> Triton X-100 lysates of BT-549 and MDA-MB 231 cells incubated with DMSO (-) or 100nM nilotinib (+) were immunoprecipitated with an anti-CST1 antibody that recognizes SRC, FYN and YES. <i>In vitro</i> kinase assay to test SRC activity was performed using enolase as substrate and P<sup>32</sup>-labeled ATP. P<sup>32</sup> incorporation by enolase was detected by autoradiography. Src and tubulin are used as loading control. Densitometry quantification normalized to tubulin is shown.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352534, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g004", "stats"=>{"downloads"=>1, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nilotinib_effect_on_ABL_and_SRC_tyrosine_kinase_activity_/1352534", "title"=>"Nilotinib effect on ABL and SRC tyrosine kinase activity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984402"], "description"=>"<p>BT-549 cells <b>(A, B)</b> and MDA-MB 231 <b>(C, D)</b> were serum-starved (0.5% serum) overnight, then plated on Oregon Green 488 gelatin and incubated with DMSO, 100nM nilotinib, 200ng/ml EGF or EGF+nilotinb for 3h. After fixation, actin cytoskeleton morphology and gelatin degradation by cells were analyzed as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118854#pone.0118854.g001\" target=\"_blank\">Fig. 1A</a>. Scale bars: 20μm. Results are the mean ± SEM, *p<0.05 compared to DMSO-treated cells. <b>(E)</b> Tyrosine phosphorylation profile and phosphorylated MAPK levels in Triton X-100 lysates from BT-549 and MDA-MB 231 cells incubated with DMSO, 100nM nilotinib or 200ng/ml EGF were assayed as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118854#pone.0118854.g004\" target=\"_blank\">Fig. 4</a>. Tubulin was used as loading control. Molecular weights (kDa) are indicated on the left.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352539, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g005", "stats"=>{"downloads"=>4, "page_views"=>30, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_HB_EGF_autocrine_loop_is_not_regulated_by_the_ABL_kinase_in_BT_549_cells_/1352539", "title"=>"The HB-EGF autocrine loop is not regulated by the ABL kinase in BT-549 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/1984403"], "description"=>"<p><b>(A, B)</b> Effect of nilotinib on BT-549 and MDA-MB 231 cell area. The area of 100 BT-549 (A) and MDA-MB 231 (B) cells plated on Oregon Green 488 gelatin was measured after incubation with DMSO or 100nM nilotinib and F-actin staining. Results are the mean ± SEM relative to control. *p<0.05 compared to DMSO-treated cells. Scale bar: 20μm. <b>(C, D)</b> Degradation area of 100 BT-549 (C) and MDA-MB 231 (D) cells incubated with DMSO, 100nM nilotinib, 2μg/ml C3, 100μM NSC23766 or 25μM ITX3 for 3h were measured as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118854#pone.0118854.g001\" target=\"_blank\">Fig. 1A</a>. Results are the mean ± SEM, *p<0.05 compared to DMSO-treated cells.</p>", "links"=>[], "tags"=>["matrix degradation", "bt", "ABL inhibitors", "Myeloid leukemia", "Tyrosine Kinase Inhibitor Nilotinib", "TN breast cancers", "Different Triple", "ABL Tyrosine Kinase Inhibition Variable Effects", "Invasive Properties", "Cell lines", "cancer cells", "carcinoma cells", "ABL kinase activity", "tumors display", "EGF secretion", "future therapies", "ABL inhibition", "breast cancer", "breast cancer cell lines", "ABL expression", "TN breast cancer cell lines", "ABL activity", "nilotinib effect", "extracellular matrix degradation"], "article_id"=>1352540, "categories"=>["Uncategorised"], "users"=>["Clément Chevalier", "Aude Cannet", "Simon Descamps", "Audrey Sirvent", "Valérie Simon", "Serge Roche", "Christine Benistant"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0118854.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_nilotinib_and_RHO_inhibitors_on_cell_area_and_matrix_degradation_/1352540", "title"=>"Effect of nilotinib and RHO inhibitors on cell area and matrix degradation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-24 03:16:37"}

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  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"8", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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