Browsing by Author "Schaible, Niccole"

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Adipokine Leptin Co-operates With Mechanosensitive Ca2 +-Channels and Triggers Actomyosin-Mediated Motility of Breast Epithelial Cells
(2021-01-06) Acheva, Anna; Kärki, Tytti; Schaible, Niccole; Krishnan, Ramaswamy; Tojkander, Sari
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
In postmenopausal women, a major risk factor for the development of breast cancer is obesity. In particular, the adipose tissue-derived adipokine leptin has been strongly linked to tumor cell proliferation, migration, and metastasis, but the underlying mechanisms remain unclear. Here we show that treatment of normal mammary epithelial cells with leptin induces EMT-like features characterized by higher cellular migration speeds, loss of structural ordering of 3D-mammo spheres, and enhancement of epithelial traction forces. Mechanistically, leptin triggers the phosphorylation of myosin light chain kinase-2 (MLC-2) through the interdependent activity of leptin receptor and Ca2+ channels. These data provide evidence that leptin-activated leptin receptors, in co-operation with mechanosensitive Ca2+ channels, play a role in the development of breast carcinomas through the regulation of actomyosin dynamics.
Cytokeratin 5 determines maturation of the mammary myoepithelium
(2021-05-21) Deckwirth, Vivi; Rajakylä, Eeva Kaisa; Cattavarayane, Sandhanakrishnan; Acheva, Anna; Schaible, Niccole; Krishnan, Ramaswamy; Valle-Delgado, Juan José; Österberg, Monika; Björkenheim, Pia; Sukura, Antti; Tojkander, Sari
A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
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.