A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Tumor promoter PMA enhances kindlin-2 and decreases vimentin recruitment into cell adhesion sites
Tekijät: Salmela M, Rappu P, Lilja J, Niskanen H, Taipalus E, Jokinen J, Heino J
Kustantaja: PERGAMON-ELSEVIER SCIENCE LTD
Julkaisuvuosi: 2016
Journal: International Journal of Biochemistry and Cell Biology
Tietokannassa oleva lehden nimi: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Lehden akronyymi: INT J BIOCHEM CELL B
Vuosikerta: 78
Aloitussivu: 22
Lopetussivu: 30
Sivujen määrä: 9
ISSN: 1357-2725
DOI: https://doi.org/10.1016/j.biocel.2016.06.017
Tiivistelmä
Phorbol diester PMA (phorbol 12-myristate 13-acetate) is a well-known promoter of tumor progression. PMA also regulates cell adhesion by several mechanisms including conformational activation of integrins and integrin clustering. Here, PMA was shown to induce lamellipodia formation and reorganization of the adhesion sites as well as actin and vimentin filaments independently of integrin preactivation. To further analyze the mechanism of PMA action, the protein composition in the alpha 1 beta 1 integrin/collagen IV adhesion sites was analyzed by mass spectrometry and proteomics. In four independent experiments we observed the reduced recruitment of vimentin in relation to integrin alpha 1 subunit. This was in full agreement with the fact that we also detected the retraction of vimentin from cell adhesions by confocal microscopy. Furthermore, the accumulation of kindlin-2 into cell adhesions was significantly increased after PMA treatment. Kindlin-2 siRNA inhibited cell spreading as well as the formation of actin fibrils and cell adhesions, but did not prevent the effect of PMA on lamellipodia formation. Thus, kindlin-2 recruitment was considered to be a consequence rather than the primary cause for the loss of connection between vimentin and the adhesion sites. (C) 2016 Elsevier Ltd. All rights reserved.
Phorbol diester PMA (phorbol 12-myristate 13-acetate) is a well-known promoter of tumor progression. PMA also regulates cell adhesion by several mechanisms including conformational activation of integrins and integrin clustering. Here, PMA was shown to induce lamellipodia formation and reorganization of the adhesion sites as well as actin and vimentin filaments independently of integrin preactivation. To further analyze the mechanism of PMA action, the protein composition in the alpha 1 beta 1 integrin/collagen IV adhesion sites was analyzed by mass spectrometry and proteomics. In four independent experiments we observed the reduced recruitment of vimentin in relation to integrin alpha 1 subunit. This was in full agreement with the fact that we also detected the retraction of vimentin from cell adhesions by confocal microscopy. Furthermore, the accumulation of kindlin-2 into cell adhesions was significantly increased after PMA treatment. Kindlin-2 siRNA inhibited cell spreading as well as the formation of actin fibrils and cell adhesions, but did not prevent the effect of PMA on lamellipodia formation. Thus, kindlin-2 recruitment was considered to be a consequence rather than the primary cause for the loss of connection between vimentin and the adhesion sites. (C) 2016 Elsevier Ltd. All rights reserved.
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