The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells
Abstract Background The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane and glycosylated protein, which is overexpressed in many neoplasms. However, EpCAM has no known ligand partners and the mechanisms by which it functions are not fully understood. Aim This study was performed...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-05-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1498 |
| _version_ | 1811248725058650112 |
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| author | Saad Misfer Al‐Qahtani Salah Eldin Gadalla Min Guo Christer Ericsson Daniel Hägerstrand Monica Nistér |
| author_facet | Saad Misfer Al‐Qahtani Salah Eldin Gadalla Min Guo Christer Ericsson Daniel Hägerstrand Monica Nistér |
| author_sort | Saad Misfer Al‐Qahtani |
| collection | DOAJ |
| description | Abstract Background The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane and glycosylated protein, which is overexpressed in many neoplasms. However, EpCAM has no known ligand partners and the mechanisms by which it functions are not fully understood. Aim This study was performed to discover novel partners of EpCAM, which may provide a better understanding of its functions. Methods The membrane fraction of the ERα+ noninvasive breast cancer cell line ZR‐75‐1 and MCF‐7 was extracted and followed by co‐immunoprecipitation of EpCAM using C‐10, a mouse monoclonal antibody raised against amino acids 24–93 of the EpCAM molecule. As a negative control, MDA‐MB‐231 and Hs578T were used since they express a negligible amount of EpCAM and are known as EpCAM−/low ERα−/low invasive and tumorigenic breast cancer cell lines. Results Annexin A2 (ANXA2) was found to be selectively and differentially co‐immunoprecipitated with EpCAM in the ERα+ breast cancer cells MCF‐7 and ZR‐75‐1. ANXA2 is a multifunctional protein and known to act as a co‐receptor for tissue plasminogen activator (tPA) on the surface of endothelial and cancer cells, thereby affecting fibrinolytic activity and neoangiogenesis as well as invasive and metastatic properties. In this study, the association between EpCAM and ANXA2 was found to affect the activity of tPA. Conclusion This study concludes that ANXA2 co‐localizes with EpCAM at the plasma membrane, and the co‐localization may have functional implications. Data suggest that EpCAM supports ANXA2 to function as a co‐receptor for the tPA, and that EpCAM has a regulatory function on the expression and subcellular localization of ANXA2. |
| first_indexed | 2024-04-12T15:34:12Z |
| format | Article |
| id | doaj.art-1dde98e1596c4fbf9811565c453e4b7f |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-04-12T15:34:12Z |
| publishDate | 2022-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-1dde98e1596c4fbf9811565c453e4b7f2022-12-22T03:27:00ZengWileyCancer Reports2573-83482022-05-0155n/an/a10.1002/cnr2.1498The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cellsSaad Misfer Al‐Qahtani0Salah Eldin Gadalla1Min Guo2Christer Ericsson3Daniel Hägerstrand4Monica Nistér5Department of Oncology‐Pathology Karolinska Institutet Stockholm SwedenDepartment of Oncology‐Pathology Karolinska Institutet Stockholm SwedenDepartment of Oncology‐Pathology Karolinska Institutet Stockholm SwedeniCellate Medical AB Stockholm SwedenDepartment of Oncology‐Pathology Karolinska Institutet Stockholm SwedenDepartment of Oncology‐Pathology Karolinska Institutet Stockholm SwedenAbstract Background The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane and glycosylated protein, which is overexpressed in many neoplasms. However, EpCAM has no known ligand partners and the mechanisms by which it functions are not fully understood. Aim This study was performed to discover novel partners of EpCAM, which may provide a better understanding of its functions. Methods The membrane fraction of the ERα+ noninvasive breast cancer cell line ZR‐75‐1 and MCF‐7 was extracted and followed by co‐immunoprecipitation of EpCAM using C‐10, a mouse monoclonal antibody raised against amino acids 24–93 of the EpCAM molecule. As a negative control, MDA‐MB‐231 and Hs578T were used since they express a negligible amount of EpCAM and are known as EpCAM−/low ERα−/low invasive and tumorigenic breast cancer cell lines. Results Annexin A2 (ANXA2) was found to be selectively and differentially co‐immunoprecipitated with EpCAM in the ERα+ breast cancer cells MCF‐7 and ZR‐75‐1. ANXA2 is a multifunctional protein and known to act as a co‐receptor for tissue plasminogen activator (tPA) on the surface of endothelial and cancer cells, thereby affecting fibrinolytic activity and neoangiogenesis as well as invasive and metastatic properties. In this study, the association between EpCAM and ANXA2 was found to affect the activity of tPA. Conclusion This study concludes that ANXA2 co‐localizes with EpCAM at the plasma membrane, and the co‐localization may have functional implications. Data suggest that EpCAM supports ANXA2 to function as a co‐receptor for the tPA, and that EpCAM has a regulatory function on the expression and subcellular localization of ANXA2.https://doi.org/10.1002/cnr2.1498ANXA2breast cancerEpCAMmolecular pathologytPA |
| spellingShingle | Saad Misfer Al‐Qahtani Salah Eldin Gadalla Min Guo Christer Ericsson Daniel Hägerstrand Monica Nistér The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells Cancer Reports ANXA2 breast cancer EpCAM molecular pathology tPA |
| title | The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells |
| title_full | The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells |
| title_fullStr | The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells |
| title_full_unstemmed | The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells |
| title_short | The association between Annexin A2 and epithelial cell adhesion molecule in breast cancer cells |
| title_sort | association between annexin a2 and epithelial cell adhesion molecule in breast cancer cells |
| topic | ANXA2 breast cancer EpCAM molecular pathology tPA |
| url | https://doi.org/10.1002/cnr2.1498 |
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