G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to...
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| Veröffentlicht in: | Cancers 2018-09, Vol.10 (9), p.325 |
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| creator | Madrazo, Elena Ruano, David Abad, Lorea Alonso-Gómez, Estefanía Sánchez-Valdepeñas, Carmen González-Murillo, África Ramírez, Manuel Redondo-Muñoz, Javier |
| description | Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion reduced slightly F-actin polymerization. Similarly to the transendothelial migration, G9a inhibition impaired the cell migration induced by the integrin VLA-4 (α4β1) of primary cells and ALL cell lines through narrow spaces in vitro. Our results suggest a cellular connection between G9a and VLA-4, which underlies novel functions of G9a during ALL cell migration. |
| doi_str_mv | 10.3390/cancers10090325 |
| format | Article |
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As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion reduced slightly F-actin polymerization. Similarly to the transendothelial migration, G9a inhibition impaired the cell migration induced by the integrin VLA-4 (α4β1) of primary cells and ALL cell lines through narrow spaces in vitro. Our results suggest a cellular connection between G9a and VLA-4, which underlies novel functions of G9a during ALL cell migration.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers10090325</identifier><identifier>PMID: 30213075</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Actin ; Acute lymphoblastic leukemia ; Bone marrow ; Cancer ; Cell adhesion & migration ; Cell migration ; Children ; Cytoskeleton ; Enzymes ; Epigenetics ; Gene expression ; Gene silencing ; Histone methyltransferase ; Immunology ; Leukemia ; Lymphatic leukemia ; Medical prognosis ; Nuclei ; Pediatrics ; Phenotypes ; Polymerization ; Therapeutic applications ; Trends ; VLA-4 antigen</subject><ispartof>Cancers, 2018-09, Vol.10 (9), p.325</ispartof><rights>2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 by the authors. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-90315f416321fa7e33beb98f9cf399f02331cd132bb5bd9b85a8ed7754a3ff643</citedby><cites>FETCH-LOGICAL-c421t-90315f416321fa7e33beb98f9cf399f02331cd132bb5bd9b85a8ed7754a3ff643</cites><orcidid>0000-0002-5261-8270 ; 0000-0002-0404-572X ; 0000-0003-0607-2171 ; 0000-0003-0332-6973</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162492/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162492/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30213075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madrazo, Elena</creatorcontrib><creatorcontrib>Ruano, David</creatorcontrib><creatorcontrib>Abad, Lorea</creatorcontrib><creatorcontrib>Alonso-Gómez, Estefanía</creatorcontrib><creatorcontrib>Sánchez-Valdepeñas, Carmen</creatorcontrib><creatorcontrib>González-Murillo, África</creatorcontrib><creatorcontrib>Ramírez, Manuel</creatorcontrib><creatorcontrib>Redondo-Muñoz, Javier</creatorcontrib><title>G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion reduced slightly F-actin polymerization. Similarly to the transendothelial migration, G9a inhibition impaired the cell migration induced by the integrin VLA-4 (α4β1) of primary cells and ALL cell lines through narrow spaces in vitro. Our results suggest a cellular connection between G9a and VLA-4, which underlies novel functions of G9a during ALL cell migration.</description><subject>Actin</subject><subject>Acute lymphoblastic leukemia</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cell adhesion & migration</subject><subject>Cell migration</subject><subject>Children</subject><subject>Cytoskeleton</subject><subject>Enzymes</subject><subject>Epigenetics</subject><subject>Gene expression</subject><subject>Gene silencing</subject><subject>Histone methyltransferase</subject><subject>Immunology</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Medical prognosis</subject><subject>Nuclei</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Polymerization</subject><subject>Therapeutic applications</subject><subject>Trends</subject><subject>VLA-4 antigen</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1v1DAQxS0EolXpmRuyxIVLWn_E8fqCtFpBqRTEBbhajjPeuCT2Yjug_vd41Q-V-mKP5vnN_PQQekvJBeeKXFoTLKRMCVGEM_ECnTIiWdN1qn355H2CznO-IfVwTmUnX6MTThjlRIpTFK-UwbuYEsymQMZ_fZnwz37btPg6FNgnH7AJYy3cvEKdl3GZAH_1-2SKjwFHh3eTn8cpxhFv7VoA97fLYYrDbHLxFvew_oLF1ykwz_kNeuXMnOH8_j5DPz5_-r770vTfrq53276xLaOlqUBUuJZ2nFFnJHA-wKA2TlnHlXKEVRQ7Us6GQQyjGjbCbGCUUrSGO9e1_Ax9vPM9rMMCo4VQkpn1IfnFpFsdjdf_d4Kf9D7-0R3tWKtYNfhwb5Di7xVy0YvPtiKYAHHNmlEiiFBKHKXvn0lv4ppCxasqJqlUG3Lc6PJOZVPMOYF7XIYSfcxTP8uz_nj3lOFR_5Ae_wdmmZz-</recordid><startdate>20180912</startdate><enddate>20180912</enddate><creator>Madrazo, Elena</creator><creator>Ruano, David</creator><creator>Abad, Lorea</creator><creator>Alonso-Gómez, Estefanía</creator><creator>Sánchez-Valdepeñas, Carmen</creator><creator>González-Murillo, África</creator><creator>Ramírez, Manuel</creator><creator>Redondo-Muñoz, Javier</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5261-8270</orcidid><orcidid>https://orcid.org/0000-0002-0404-572X</orcidid><orcidid>https://orcid.org/0000-0003-0607-2171</orcidid><orcidid>https://orcid.org/0000-0003-0332-6973</orcidid></search><sort><creationdate>20180912</creationdate><title>G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells</title><author>Madrazo, Elena ; Ruano, David ; Abad, Lorea ; Alonso-Gómez, Estefanía ; Sánchez-Valdepeñas, Carmen ; González-Murillo, África ; Ramírez, Manuel ; Redondo-Muñoz, Javier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-90315f416321fa7e33beb98f9cf399f02331cd132bb5bd9b85a8ed7754a3ff643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Actin</topic><topic>Acute lymphoblastic leukemia</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Cell adhesion & migration</topic><topic>Cell migration</topic><topic>Children</topic><topic>Cytoskeleton</topic><topic>Enzymes</topic><topic>Epigenetics</topic><topic>Gene expression</topic><topic>Gene silencing</topic><topic>Histone methyltransferase</topic><topic>Immunology</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Medical prognosis</topic><topic>Nuclei</topic><topic>Pediatrics</topic><topic>Phenotypes</topic><topic>Polymerization</topic><topic>Therapeutic applications</topic><topic>Trends</topic><topic>VLA-4 antigen</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Madrazo, Elena</creatorcontrib><creatorcontrib>Ruano, David</creatorcontrib><creatorcontrib>Abad, Lorea</creatorcontrib><creatorcontrib>Alonso-Gómez, Estefanía</creatorcontrib><creatorcontrib>Sánchez-Valdepeñas, Carmen</creatorcontrib><creatorcontrib>González-Murillo, África</creatorcontrib><creatorcontrib>Ramírez, Manuel</creatorcontrib><creatorcontrib>Redondo-Muñoz, Javier</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Madrazo, Elena</au><au>Ruano, David</au><au>Abad, Lorea</au><au>Alonso-Gómez, Estefanía</au><au>Sánchez-Valdepeñas, Carmen</au><au>González-Murillo, África</au><au>Ramírez, Manuel</au><au>Redondo-Muñoz, Javier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2018-09-12</date><risdate>2018</risdate><volume>10</volume><issue>9</issue><spage>325</spage><pages>325-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion reduced slightly F-actin polymerization. Similarly to the transendothelial migration, G9a inhibition impaired the cell migration induced by the integrin VLA-4 (α4β1) of primary cells and ALL cell lines through narrow spaces in vitro. Our results suggest a cellular connection between G9a and VLA-4, which underlies novel functions of G9a during ALL cell migration.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30213075</pmid><doi>10.3390/cancers10090325</doi><orcidid>https://orcid.org/0000-0002-5261-8270</orcidid><orcidid>https://orcid.org/0000-0002-0404-572X</orcidid><orcidid>https://orcid.org/0000-0003-0607-2171</orcidid><orcidid>https://orcid.org/0000-0003-0332-6973</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Actin Acute lymphoblastic leukemia Bone marrow Cancer Cell adhesion & migration Cell migration Children Cytoskeleton Enzymes Epigenetics Gene expression Gene silencing Histone methyltransferase Immunology Leukemia Lymphatic leukemia Medical prognosis Nuclei Pediatrics Phenotypes Polymerization Therapeutic applications Trends VLA-4 antigen |
| title | G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells |
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