Cytokeratin 5 determines maturation of the mammary myoepithelium
Summary: At invasion, transformed mammary epithelial cells expand into the stroma through a disrupted myoepithelial (ME) cell layer and basement membrane (BM). The intact ME cell layer has thus been suggested to act as a barrier against invasion. Here, we investigate the mechanisms behind the disrup...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221003813 |
| _version_ | 1818594682508148736 |
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| author | Vivi Deckwirth Eeva Kaisa Rajakylä Sandhanakrishnan Cattavarayane Anna Acheva Niccole Schaible Ramaswamy Krishnan Juan José Valle-Delgado Monika Österberg Pia Björkenheim Antti Sukura Sari Tojkander |
| author_facet | Vivi Deckwirth Eeva Kaisa Rajakylä Sandhanakrishnan Cattavarayane Anna Acheva Niccole Schaible Ramaswamy Krishnan Juan José Valle-Delgado Monika Österberg Pia Björkenheim Antti Sukura Sari Tojkander |
| author_sort | Vivi Deckwirth |
| collection | DOAJ |
| description | Summary: At invasion, transformed mammary epithelial cells expand into the stroma through a disrupted myoepithelial (ME) cell layer and basement membrane (BM). The intact ME cell layer has thus been suggested to act as a barrier against invasion. Here, we investigate the mechanisms behind the disruption of ME cell layer. We show that the expression of basal/ME proteins CK5, CK14, and α-SMA altered along increasing grade of malignancy, and their loss affected the maintenance of organotypic 3D mammary architecture. Furthermore, our data suggests that loss of CK5 prior to invasive stage causes decreased levels of Zinc finger protein SNAI2 (SLUG), a key regulator of the mammary epithelial cell lineage determination. Consequently, a differentiation bias toward luminal epithelial cell type was detected with loss of mature, α-SMA-expressing ME cells and reduced deposition of basement membrane protein laminin-5. Therefore, our data discloses the central role of CK5 in mammary epithelial differentiation and maintenance of normal ME layer. |
| first_indexed | 2024-12-16T11:04:00Z |
| format | Article |
| id | doaj.art-48a097948b3d46a282c483d28a63f2ea |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T11:04:00Z |
| publishDate | 2021-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-48a097948b3d46a282c483d28a63f2ea2022-12-21T22:33:54ZengElsevieriScience2589-00422021-05-01245102413Cytokeratin 5 determines maturation of the mammary myoepitheliumVivi Deckwirth0Eeva Kaisa Rajakylä1Sandhanakrishnan Cattavarayane2Anna Acheva3Niccole Schaible4Ramaswamy Krishnan5Juan José Valle-Delgado6Monika Österberg7Pia Björkenheim8Antti Sukura9Sari Tojkander10Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, FinlandSection of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, FinlandSection of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, FinlandSection of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, FinlandBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USABeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USADepartment of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo 00076, FinlandDepartment of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo 00076, FinlandVeterinary Teaching Hospital, University of Helsinki, Helsinki 00014, FinlandSection of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, FinlandSection of Pathology, Department of Veterinary Biosciences, University of Helsinki, Agnes Sjöberginkatu 2, Helsinki 00014, Finland; Corresponding authorSummary: At invasion, transformed mammary epithelial cells expand into the stroma through a disrupted myoepithelial (ME) cell layer and basement membrane (BM). The intact ME cell layer has thus been suggested to act as a barrier against invasion. Here, we investigate the mechanisms behind the disruption of ME cell layer. We show that the expression of basal/ME proteins CK5, CK14, and α-SMA altered along increasing grade of malignancy, and their loss affected the maintenance of organotypic 3D mammary architecture. Furthermore, our data suggests that loss of CK5 prior to invasive stage causes decreased levels of Zinc finger protein SNAI2 (SLUG), a key regulator of the mammary epithelial cell lineage determination. Consequently, a differentiation bias toward luminal epithelial cell type was detected with loss of mature, α-SMA-expressing ME cells and reduced deposition of basement membrane protein laminin-5. Therefore, our data discloses the central role of CK5 in mammary epithelial differentiation and maintenance of normal ME layer.http://www.sciencedirect.com/science/article/pii/S2589004221003813Cell BiologyDevelopmental BiologyBiophysics |
| spellingShingle | Vivi Deckwirth Eeva Kaisa Rajakylä Sandhanakrishnan Cattavarayane Anna Acheva Niccole Schaible Ramaswamy Krishnan Juan José Valle-Delgado Monika Österberg Pia Björkenheim Antti Sukura Sari Tojkander Cytokeratin 5 determines maturation of the mammary myoepithelium iScience Cell Biology Developmental Biology Biophysics |
| title | Cytokeratin 5 determines maturation of the mammary myoepithelium |
| title_full | Cytokeratin 5 determines maturation of the mammary myoepithelium |
| title_fullStr | Cytokeratin 5 determines maturation of the mammary myoepithelium |
| title_full_unstemmed | Cytokeratin 5 determines maturation of the mammary myoepithelium |
| title_short | Cytokeratin 5 determines maturation of the mammary myoepithelium |
| title_sort | cytokeratin 5 determines maturation of the mammary myoepithelium |
| topic | Cell Biology Developmental Biology Biophysics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221003813 |
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