Adipokine Leptin Co-operates With Mechanosensitive Ca2 +-Channels and Triggers Actomyosin-Mediated Motility of Breast Epithelial Cells

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.

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Analysis of Progestin Effects on Hepatocyte Growth Factor Signaling Pathways in Relation to Proliferation and Alveolar Morphogenesis of Normal Mammary Epithelial Cells in Vitro

10.21236/ada416749 ◽

2003 ◽

Author(s):

Kyle T. Smith

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Hepatocyte Growth Factor ◽

Signaling Pathways ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Growth Factor Signaling ◽

Hepatocyte Growth ◽

Normal Mammary Epithelial

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The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis

Journal of Cell Science ◽

10.1242/jcs.110.1.55 ◽

1997 ◽

Vol 110 (1) ◽

pp. 55-63 ◽

Cited By ~ 7

Author(s):

S. Stahl ◽

S. Weitzman ◽

J.C. Jones

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Mammary Epithelial Cells ◽

Branching Morphogenesis ◽

Mammary Epithelial ◽

Breast Epithelial Cell ◽

Epithelial Tissue ◽

Laminin 5 ◽

Normal Mammary Epithelial

In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin ‘backbone’, play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.

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