title: Scattering of MCF7 cells by heregulin ß-1 depends on the MEK and p38 MAP kinase pathway.
abstract: Heregulin (HRG) β1 signaling promotes scattering of MCF7 cells by inducing breakdown of adherens and tight junctions. Here, we show that stimulation with HRG-β1 causes the F-actin backbone of junctions to destabilize prior to the loss of adherent proteins and scattering of the cells. The adherent proteins dissociate and translocate from cell-cell junctions to the cytosol. Moreover, using inhibitors we show that the MEK1 pathway is required for the disappearance of F-actin from junctions and p38 MAP kinase activity is essential for scattering of the cells. Upon treatment with a p38 MAP kinase inhibitor, adherens junction complexes immediately reassemble, most likely in the cytoplasm, and move to the plasma membrane in cells dissociated by HRG-β1 stimulation. Subsequently, tight junction complexes form, most likely in the cytoplasm, and move to the plasma membrane. Thus, the p38 MAP kinase inhibitor causes a re-aggregation of scattered cells, even in the presence of HRG-β1. These results suggest that p38 MAP kinase signaling to adherens junction proteins regulates cell aggregation, providing a novel understanding of the regulation of cell-cell adhesion.
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan, Republic of China.
authors: Rintaro
authors: R
authors: Okoshi
authors: Chung-Li
authors: CL
authors: Shu
authors: Sayoko
authors: S
authors: Ihara
authors: Yasuhisa
authors: Y
authors: Fukui
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D020890:Neuregulin-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000199:Actins; D020890:Neuregulin-1; C087230:heregulin beta1; D048051:p38 Mitogen-Activated Protein Kinases