Acheva Anna, Kärki Tytti, Schaible Niccole, Krishnan Ramaswamy, Tojkander Sari
Section of Pathology, Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Department of Applied Physics, School of Science, Aalto University, Espoo, Finland.
Front Cell Dev Biol. 2021 Jan 6;8:607038. doi: 10.3389/fcell.2020.607038. eCollection 2020.
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 Ca channels. These data provide evidence that leptin-activated leptin receptors, in co-operation with mechanosensitive Ca channels, play a role in the development of breast carcinomas through the regulation of actomyosin dynamics.
在绝经后女性中，肥胖是乳腺癌发生的主要危险因素。特别是，脂肪组织来源的脂肪因子瘦素与肿瘤细胞增殖、迁移和转移密切相关，但其潜在机制仍不清楚。在这里，我们表明用瘦素处理正常乳腺上皮细胞会诱导类似上皮-间质转化（EMT）的特征，其特点是细胞迁移速度加快、三维乳腺球结构有序性丧失以及上皮牵引力增强。从机制上讲，瘦素通过瘦素受体和钙通道的相互依存活性触发肌球蛋白轻链激酶-2（MLC-2）的磷酸化。这些数据提供了证据，表明瘦素激活的瘦素受体与机械敏感钙通道协同作用，通过调节肌动球蛋白动力学在乳腺癌的发生发展中发挥作用。
