Cytokeratin 5 determines maturation of the mammary myoepithelium

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*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)
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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.

Original languageEnglish
Article number102413
Number of pages16
JournaliScience
Volume24
Issue number5
DOIs
Publication statusPublished - 21 May 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • Biophysics
  • Cell Biology
  • Developmental Biology

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