The cooperation between hMena overexpression and HER2 signalling in breast cancer
hMena and the epithelial specific isoform hMena(11a) are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family an...
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| Veröffentlicht in: | PloS one 2010-12, Vol.5 (12), p.e15852-e15852 |
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| creator | Di Modugno, Francesca Mottolese, Marcella DeMonte, Lucia Trono, Paola Balsamo, Michele Conidi, Andrea Melucci, Elisa Terrenato, Irene Belleudi, Francesca Torrisi, Maria Rosaria Alessio, Massimo Santoni, Angela Nisticò, Paola |
| description | hMena and the epithelial specific isoform hMena(11a) are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family and hMena/hMena(11a) in breast cancer. The aim of this study was to determine whether the hMena/hMena(11a) overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena(11a) expression and hMena(11a) phosphorylation. On the other hand, hMena/hMena(11a) knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena(11a) knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena(11a) as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients. |
| doi_str_mv | 10.1371/journal.pone.0015852 |
| format | Article |
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EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family and hMena/hMena(11a) in breast cancer. The aim of this study was to determine whether the hMena/hMena(11a) overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena(11a) expression and hMena(11a) phosphorylation. On the other hand, hMena/hMena(11a) knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena(11a) knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena(11a) as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0015852</identifier><identifier>PMID: 21209853</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Actin ; Adult ; Aged ; Aged, 80 and over ; AKT protein ; Biochemistry ; Biology ; Breast cancer ; Breast Neoplasms - metabolism ; Cancer ; Cancer research ; Cancer therapies ; Cancer treatment ; Care and treatment ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Cloning ; Crosstalk ; Cytoskeleton ; Development and progression ; Disease Progression ; Epidermal growth factors ; ErbB protein ; ErbB-2 protein ; Female ; Gene Expression Regulation ; Growth factors ; Humans ; Immunology ; Kinases ; Laboratories ; MAP kinase ; MAP Kinase Signaling System ; Medical prognosis ; Medicine ; Metastasis ; Microfilament Proteins - metabolism ; Middle Aged ; Muscle proteins ; Patients ; Peripheral neuropathy ; Phosphatase ; Phosphorylation ; Proteins ; Proteomics ; Receptor, ErbB-2 - metabolism ; Regulatory proteins ; Rodents ; Signal Transduction ; Signaling ; Subgroups ; Transfection ; Tumor cell lines ; Tumors</subject><ispartof>PloS one, 2010-12, Vol.5 (12), p.e15852-e15852</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Di Modugno et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Di Modugno et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-1e4f3e61ab955b73ab4a93c3a7d7516390dda621a70ec5cffcf31620d871655b3</citedby><cites>FETCH-LOGICAL-c691t-1e4f3e61ab955b73ab4a93c3a7d7516390dda621a70ec5cffcf31620d871655b3</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/PMC3012725/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012725/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21209853$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Means, Robert E.</contributor><creatorcontrib>Di Modugno, Francesca</creatorcontrib><creatorcontrib>Mottolese, Marcella</creatorcontrib><creatorcontrib>DeMonte, Lucia</creatorcontrib><creatorcontrib>Trono, Paola</creatorcontrib><creatorcontrib>Balsamo, Michele</creatorcontrib><creatorcontrib>Conidi, Andrea</creatorcontrib><creatorcontrib>Melucci, Elisa</creatorcontrib><creatorcontrib>Terrenato, Irene</creatorcontrib><creatorcontrib>Belleudi, Francesca</creatorcontrib><creatorcontrib>Torrisi, Maria Rosaria</creatorcontrib><creatorcontrib>Alessio, Massimo</creatorcontrib><creatorcontrib>Santoni, Angela</creatorcontrib><creatorcontrib>Nisticò, Paola</creatorcontrib><title>The cooperation between hMena overexpression and HER2 signalling in breast cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>hMena and the epithelial specific isoform hMena(11a) are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family and hMena/hMena(11a) in breast cancer. The aim of this study was to determine whether the hMena/hMena(11a) overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena(11a) expression and hMena(11a) phosphorylation. On the other hand, hMena/hMena(11a) knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena(11a) knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena(11a) as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients.</description><subject>Actin</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>AKT protein</subject><subject>Biochemistry</subject><subject>Biology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cancer treatment</subject><subject>Care and treatment</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cloning</subject><subject>Crosstalk</subject><subject>Cytoskeleton</subject><subject>Development and progression</subject><subject>Disease Progression</subject><subject>Epidermal growth factors</subject><subject>ErbB protein</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Gene Expression Regulation</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Immunology</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>MAP kinase</subject><subject>MAP Kinase Signaling System</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Metastasis</subject><subject>Microfilament Proteins - 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Academic</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>Di Modugno, Francesca</au><au>Mottolese, Marcella</au><au>DeMonte, Lucia</au><au>Trono, Paola</au><au>Balsamo, Michele</au><au>Conidi, Andrea</au><au>Melucci, Elisa</au><au>Terrenato, Irene</au><au>Belleudi, Francesca</au><au>Torrisi, Maria Rosaria</au><au>Alessio, Massimo</au><au>Santoni, Angela</au><au>Nisticò, Paola</au><au>Means, Robert E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The cooperation between hMena overexpression and HER2 signalling in breast cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-12-30</date><risdate>2010</risdate><volume>5</volume><issue>12</issue><spage>e15852</spage><epage>e15852</epage><pages>e15852-e15852</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>hMena and the epithelial specific isoform hMena(11a) are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena(11a) expression and phosphorylates hMena(11a), suggesting cross-talk between the ErbB receptor family and hMena/hMena(11a) in breast cancer. The aim of this study was to determine whether the hMena/hMena(11a) overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena(11a) expression and hMena(11a) phosphorylation. On the other hand, hMena/hMena(11a) knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena(11a) knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena(11a) as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21209853</pmid><doi>10.1371/journal.pone.0015852</doi><tpages>e15852</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2010-12, Vol.5 (12), p.e15852-e15852 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1296296906 |
| 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 | Actin Adult Aged Aged, 80 and over AKT protein Biochemistry Biology Breast cancer Breast Neoplasms - metabolism Cancer Cancer research Cancer therapies Cancer treatment Care and treatment Cell cycle Cell growth Cell Line, Tumor Cell Proliferation Cloning Crosstalk Cytoskeleton Development and progression Disease Progression Epidermal growth factors ErbB protein ErbB-2 protein Female Gene Expression Regulation Growth factors Humans Immunology Kinases Laboratories MAP kinase MAP Kinase Signaling System Medical prognosis Medicine Metastasis Microfilament Proteins - metabolism Middle Aged Muscle proteins Patients Peripheral neuropathy Phosphatase Phosphorylation Proteins Proteomics Receptor, ErbB-2 - metabolism Regulatory proteins Rodents Signal Transduction Signaling Subgroups Transfection Tumor cell lines Tumors |
| title | The cooperation between hMena overexpression and HER2 signalling in breast cancer |
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