Gasdermin-B promotes invasion and metastasis in breast cancer cells
Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing...
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| Veröffentlicht in: | PloS one 2014-03, Vol.9 (3), p.e90099 |
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| creator | Hergueta-Redondo, Marta Sarrió, David Molina-Crespo, Ángela Megias, Diego Mota, Alba Rojo-Sebastian, Alejandro García-Sanz, Pablo Morales, Saleta Abril, Sandra Cano, Amparo Peinado, Héctor Moreno-Bueno, Gema |
| description | Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer. |
| doi_str_mv | 10.1371/journal.pone.0090099 |
| format | Article |
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Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0090099</identifier><identifier>PMID: 24675552</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Alternative splicing ; Animal models ; Animals ; Biology and Life Sciences ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - genetics ; Breast Neoplasms - mortality ; Breast Neoplasms - pathology ; Cancer ; Carcinogenesis ; Carcinogens ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - mortality ; Carcinoma, Ductal, Breast - pathology ; Cell Line, Tumor ; Cell migration ; Cell Movement - genetics ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - metabolism ; Cervix ; Datasets as Topic ; Disease Models, Animal ; Female ; G proteins ; Gelatin - metabolism ; Gene Expression ; Genes ; Genes, Reporter ; Guanine nucleotide-binding protein ; Heat shock proteins ; Heterografts ; HSP90 Heat-Shock Proteins - metabolism ; Hsp90 protein ; Humans ; Invasiveness ; Isoforms ; Kinases ; Lymphocytes B ; Medicine and Health Sciences ; Metastases ; Metastasis ; Mice ; Middle Aged ; Molecular Imaging ; Motility ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Proteins - genetics ; Neoplasm Proteins - metabolism ; Overexpression ; Phenotype ; Prognosis ; Protein Binding ; Proteins ; Proteolysis ; Rac1 protein ; rho GTP-Binding Proteins - metabolism ; Rodents ; Skin cancer ; Tumors ; Xenografts</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e90099</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Hergueta-Redondo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Hergueta-Redondo et al 2014 Hergueta-Redondo et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4560186afc9fb78983d97f130c73acee6926353d0f6f699424685b583bfcc61f3</citedby><cites>FETCH-LOGICAL-c692t-4560186afc9fb78983d97f130c73acee6926353d0f6f699424685b583bfcc61f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967990/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967990/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24675552$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hergueta-Redondo, Marta</creatorcontrib><creatorcontrib>Sarrió, David</creatorcontrib><creatorcontrib>Molina-Crespo, Ángela</creatorcontrib><creatorcontrib>Megias, Diego</creatorcontrib><creatorcontrib>Mota, Alba</creatorcontrib><creatorcontrib>Rojo-Sebastian, Alejandro</creatorcontrib><creatorcontrib>García-Sanz, Pablo</creatorcontrib><creatorcontrib>Morales, Saleta</creatorcontrib><creatorcontrib>Abril, Sandra</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>Peinado, Héctor</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><title>Gasdermin-B promotes invasion and metastasis in breast cancer cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alternative splicing</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Carcinogens</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - mortality</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - genetics</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cervix</subject><subject>Datasets as Topic</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>G proteins</subject><subject>Gelatin - metabolism</subject><subject>Gene Expression</subject><subject>Genes</subject><subject>Genes, Reporter</subject><subject>Guanine nucleotide-binding protein</subject><subject>Heat shock proteins</subject><subject>Heterografts</subject><subject>HSP90 Heat-Shock Proteins - metabolism</subject><subject>Hsp90 protein</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Isoforms</subject><subject>Kinases</subject><subject>Lymphocytes B</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Molecular Imaging</subject><subject>Motility</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Overexpression</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Protein Binding</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Rac1 protein</subject><subject>rho GTP-Binding Proteins - metabolism</subject><subject>Rodents</subject><subject>Skin cancer</subject><subject>Tumors</subject><subject>Xenografts</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguBFx6RpkuZGWAddBxYW_LoNaZrMZGiTMcks-u8943SXKShIAklOnvPm5PAWxXOMFphw_HYb9tGrYbEL3iwQEjDFg-IcC1JXrEbk4cn-rHiS0hYhSlrGHhdndcM4pbQ-L5ZXKvUmjs5X78tdDGPIJpXO36rkgi-V78vRZJVgukO87KKBU6mV1yaW2gxDelo8smpI5tm0XhTfPn74uvxUXd9crZaX15Vmos5VQxnCLVNWC9vxVrSkF9xigjQnShsDECOU9Mgyy4RooMiWdrQlndWaYUsuipdH3d0Qkpz-nySmGHHWItoAsToSfVBbuYtuVPGXDMrJP4EQ11LF7PRgpCYEN5QKSpRqhEBQFiWcYdxpzesGgda76bV9N5peG5-jGmai8xvvNnIdbiURjIMgCLyaBGL4sTcp_6PkiVorqMp5G0BMjy5pednwlhPBWwLU4i8UjN6MToMDrIP4LOHNLAGYbH7mtdqnJFdfPv8_e_N9zr4-YTdGDXmTwrDP4JY0B5sjqGNIKRp73zmM5MHAd92QBwPLycCQ9uK06_dJd44lvwH_wOm3</recordid><startdate>20140327</startdate><enddate>20140327</enddate><creator>Hergueta-Redondo, Marta</creator><creator>Sarrió, David</creator><creator>Molina-Crespo, Ángela</creator><creator>Megias, Diego</creator><creator>Mota, Alba</creator><creator>Rojo-Sebastian, Alejandro</creator><creator>García-Sanz, Pablo</creator><creator>Morales, Saleta</creator><creator>Abril, Sandra</creator><creator>Cano, Amparo</creator><creator>Peinado, Héctor</creator><creator>Moreno-Bueno, Gema</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140327</creationdate><title>Gasdermin-B promotes invasion and metastasis in breast cancer cells</title><author>Hergueta-Redondo, Marta ; Sarrió, David ; Molina-Crespo, Ángela ; Megias, Diego ; Mota, Alba ; Rojo-Sebastian, Alejandro ; García-Sanz, Pablo ; Morales, Saleta ; Abril, Sandra ; Cano, Amparo ; Peinado, Héctor ; Moreno-Bueno, Gema</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4560186afc9fb78983d97f130c73acee6926353d0f6f699424685b583bfcc61f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alternative splicing</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>Breast Neoplasms - 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genetics</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Overexpression</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Protein Binding</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>Rac1 protein</topic><topic>rho GTP-Binding Proteins - metabolism</topic><topic>Rodents</topic><topic>Skin cancer</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hergueta-Redondo, Marta</creatorcontrib><creatorcontrib>Sarrió, David</creatorcontrib><creatorcontrib>Molina-Crespo, Ángela</creatorcontrib><creatorcontrib>Megias, Diego</creatorcontrib><creatorcontrib>Mota, Alba</creatorcontrib><creatorcontrib>Rojo-Sebastian, Alejandro</creatorcontrib><creatorcontrib>García-Sanz, Pablo</creatorcontrib><creatorcontrib>Morales, Saleta</creatorcontrib><creatorcontrib>Abril, Sandra</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>Peinado, Héctor</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hergueta-Redondo, Marta</au><au>Sarrió, David</au><au>Molina-Crespo, Ángela</au><au>Megias, Diego</au><au>Mota, Alba</au><au>Rojo-Sebastian, Alejandro</au><au>García-Sanz, Pablo</au><au>Morales, Saleta</au><au>Abril, Sandra</au><au>Cano, Amparo</au><au>Peinado, Héctor</au><au>Moreno-Bueno, Gema</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gasdermin-B promotes invasion and metastasis in breast cancer cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-03-27</date><risdate>2014</risdate><volume>9</volume><issue>3</issue><spage>e90099</spage><pages>e90099-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Gasdermin B (GSDMB) belongs to the Gasdermin protein family that comprises four members (GSDMA-D). Gasdermin B expression has been detected in some tumor types such as hepatocarcinomas, gastric and cervix cancers; and its over-expression has been related to tumor progression. At least four splicing isoforms of GSDMB have been identified, which may play differential roles in cancer. However, the implication of GSDMB in carcinogenesis and tumor progression is not well understood. Here, we uncover for the first time the functional implication of GSDMB in breast cancer. Our data shows that high levels of GSDMB expression is correlated with reduced survival and increased metastasis in breast cancer patients included in an expression dataset (>1,000 cases). We demonstrate that GSDMB is upregulated in breast carcinomas compared to normal breast tissue, being the isoform 2 (GSDMB-2) the most differentially expressed. In order to evaluate the functional role of GSDMB in breast cancer two GSDMB isoforms were studied (GSDMB-1 and GSDMB-2). The overexpression of both isoforms in the MCF7 breast carcinoma cell line promotes cell motility and invasion, while its silencing in HCC1954 breast carcinoma cells decreases the migratory and invasive phenotype. Importantly, we demonstrate that both isoforms have a differential role on the activation of Rac-1 and Cdc-42 Rho-GTPases. Moreover, our data support that GSMDB-2 induces a pro-tumorigenic and pro-metastatic behavior in mouse xenograft models as compared to GSDMB-1. Finally, we observed that although both GSDMB isoforms interact in vitro with the chaperone Hsp90, only the GSDMB-2 isoform relies on this chaperone for its stability. Taken together, our results provide for the first time evidences that GSDMB-2 induces invasion, tumor progression and metastasis in MCF7 cells and that GSDMB can be considered as a new potential prognostic marker in breast cancer.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24675552</pmid><doi>10.1371/journal.pone.0090099</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-03, Vol.9 (3), p.e90099 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1510768054 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Aged Aged, 80 and over Alternative splicing Animal models Animals Biology and Life Sciences Breast cancer Breast carcinoma Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - pathology Cancer Carcinogenesis Carcinogens Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - mortality Carcinoma, Ductal, Breast - pathology Cell Line, Tumor Cell migration Cell Movement - genetics Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - metabolism Cervix Datasets as Topic Disease Models, Animal Female G proteins Gelatin - metabolism Gene Expression Genes Genes, Reporter Guanine nucleotide-binding protein Heat shock proteins Heterografts HSP90 Heat-Shock Proteins - metabolism Hsp90 protein Humans Invasiveness Isoforms Kinases Lymphocytes B Medicine and Health Sciences Metastases Metastasis Mice Middle Aged Molecular Imaging Motility Neoplasm Grading Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Proteins - genetics Neoplasm Proteins - metabolism Overexpression Phenotype Prognosis Protein Binding Proteins Proteolysis Rac1 protein rho GTP-Binding Proteins - metabolism Rodents Skin cancer Tumors Xenografts |
| title | Gasdermin-B promotes invasion and metastasis in breast cancer cells |
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