The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer
hMena and the epithelial specific isoform hMena11a are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena11a expression and phosphorylates hMena11a, suggesting cross-talk between the ErbB receptor family and hMen...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2011
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| Online Access: | http://hdl.handle.net/1721.1/64748 |
| _version_ | 1826212979461324800 |
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| author | Di Modugno, Francesca Mottolese, Marcella DeMonte, Lucia Trono, Paola Terrenato, Irene Belleudi, Francesca Torrisi, Maria Rosaria Alessio, Massimo Santoni, Angela Nistico, Paola |
| author2 | Koch Institute for Integrative Cancer Research at MIT |
| author_facet | Koch Institute for Integrative Cancer Research at MIT Di Modugno, Francesca Mottolese, Marcella DeMonte, Lucia Trono, Paola Terrenato, Irene Belleudi, Francesca Torrisi, Maria Rosaria Alessio, Massimo Santoni, Angela Nistico, Paola |
| author_sort | Di Modugno, Francesca |
| collection | MIT |
| description | hMena and the epithelial specific isoform hMena11a are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena11a expression and phosphorylates hMena11a, suggesting cross-talk between the ErbB receptor family and hMena/hMena11a in breast cancer. The aim of this study was to determine whether the hMena/hMena11a 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/hMena11a expression and hMena11a phosphorylation. On the other hand, hMena/hMena11a 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/hMena11a knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena11a as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients. |
| first_indexed | 2024-09-23T15:41:12Z |
| format | Article |
| id | mit-1721.1/64748 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:41:12Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/647482022-09-29T15:30:09Z The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer Di Modugno, Francesca Mottolese, Marcella DeMonte, Lucia Trono, Paola Terrenato, Irene Belleudi, Francesca Torrisi, Maria Rosaria Alessio, Massimo Santoni, Angela Nistico, Paola Koch Institute for Integrative Cancer Research at MIT Balsamo, Michele Balsamo, Michele hMena and the epithelial specific isoform hMena11a are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena11a expression and phosphorylates hMena11a, suggesting cross-talk between the ErbB receptor family and hMena/hMena11a in breast cancer. The aim of this study was to determine whether the hMena/hMena11a 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/hMena11a expression and hMena11a phosphorylation. On the other hand, hMena/hMena11a 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/hMena11a knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena11a as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients. Italian Association for Cancer Research Italian Ministry of Health Italian Ministry of Health (PIO-2006 RO strategici 5/07) Virginia and D.K. Ludwig Fund for Cancer Research (Postdoctoral Fellowship) 2011-07-06T18:30:04Z 2011-07-06T18:30:04Z 2010-12 2010-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/64748 Di Modugno, Francesca et al. "The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer." PLoS ONE 5(12): e15852. en_US http://dx.doi.org/10.1371/journal.pone.0015852 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Di Modugno, Francesca Mottolese, Marcella DeMonte, Lucia Trono, Paola Terrenato, Irene Belleudi, Francesca Torrisi, Maria Rosaria Alessio, Massimo Santoni, Angela Nistico, Paola The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title | The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title_full | The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title_fullStr | The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title_full_unstemmed | The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title_short | The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer |
| title_sort | cooperation between hmena overexpression and her2 signalling in breast cancer |
| url | http://hdl.handle.net/1721.1/64748 |
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