Cytokeratin 5 determines maturation of the mammary myoepithelium
Loading...
Access rights
openAccess
Journal Title
Journal ISSN
Volume Title
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
This publication is imported from Aalto University research portal.
View publication in the Research portal
View/Open full text file from the Research portal
Other link related to publication
View publication in the Research portal
View/Open full text file from the Research portal
Other link related to publication
Date
2021-05-21
Department
Major/Subject
Mcode
Degree programme
Language
en
Pages
16
Series
iScience, Volume 24, issue 5
Abstract
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.Description
Funding Information: This work is supported by funding from the Academy of Finland , University of Helsinki , Jane and Aatos Erkko Foundation as well as Sigrid Jusélius Foundation (S.T.), and The Finnish Veterinary Foundation and The Foundation of Veterinary Research (V.D.). The Institute of Biotechnology (HiLIFE Helsinki Institute of Life Science, University of Helsinki, Finland) is acknowledged for the scanning of the IHC stained canine mammary FFPE tissue slides. OutiVapaavuori (Veterinary Teaching Hospital, University of Helsinki, Finland) is thanked for canine mammary tumor samples. LMU imaging unit (HiLIFE Helsinki) is acknowledged for the assistance in imaging-related work and TiinaPessa-Morikawa (Department of Veterinary Biosciences, University of Helsinki, Finland) is thanked for assistance in FACS-related technical aspects. Mona Zimmermann and TuuliaSavela are thanked for the assistance in cell biological assays. Raphael Ahrens is thanked for the assistance in the analysis of AFM indentation curves. This work made use of Aalto University Bioeconomy Facilities, Helsinki, Finland. Publisher Copyright: © 2021 The Author(s) Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords
Biophysics, Cell Biology, Developmental Biology
Other note
Citation
Deckwirth, V, Rajakylä, E K, Cattavarayane, S, Acheva, A, Schaible, N, Krishnan, R, Valle-Delgado, J J, Österberg, M, Björkenheim, P, Sukura, A & Tojkander, S 2021, ' Cytokeratin 5 determines maturation of the mammary myoepithelium ', iScience, vol. 24, no. 5, 102413 . https://doi.org/10.1016/j.isci.2021.102413
