کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2132970 1086731 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Requirement of the enzymatic and signaling activities of plasmin for phorbol-ester-induced scattering of colon cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Requirement of the enzymatic and signaling activities of plasmin for phorbol-ester-induced scattering of colon cancer cells
چکیده انگلیسی

Colon cancer progression is associated with the activation of protein kinase C (PKC), the downregulation of functional E-cadherin and an increased expression of the serine protease urokinase (u-PA) and its receptor (u-PAR). HT29-M6 intestinal epithelial cells represent an in vitro model to study colon cancer progression. These cells are induced to scatter and to invade by phorbol esters. Using proteolytic and cell signaling inhibitors, we show that HT29-M6 cells require plasminogen for the acquisition of the scattering response to PMA. Our results indicate that, prior to inducing a state of competency for plasminogen-dependent scattering, PMA triggers an ordered succession of events where upregulation of the activity of u-PA precedes proteolysis of u-PAR and active degradation of the extracellular matrix (ECM). These events poise HT29-M6 cells to a scatter-competent state that allows the subsequent localized proteolytic activation of plasminogen to plasmin, required for the execution of scattering. Finally, we show that, in addition to its enzymatic activity directed at the degradation of ECM, plasmin generates an intracellular signal resulting in the phosphorylation of ERK 1/2. For a full motogenic activity, plasmin requires this signal since the use of a MEK inhibitor (PD98059) specifically blocks the plasmin-dependent phase of cell scattering. Our observations suggest that plasmin exerts a dual role in PMA-induced scattering of HT29-M6 cells, one directed extracellularly to promote proteolysis of the ECM and one directed to generate intracellular signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 312, Issue 12, 15 July 2006, Pages 2203–2213
نویسندگان
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