کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6101919 1211111 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ArticleECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human hepatocellular carcinoma
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Research ArticleECT2 regulates the Rho/ERK signalling axis to promote early recurrence in human hepatocellular carcinoma
چکیده انگلیسی

Background & AimsEarly recurrence is the major obstacle for improving the outcome of patients with hepatocellular carcinoma (HCC). Therefore, identifying key molecules contributing to early HCC recurrence can enable the development of novel therapeutic strategies for the clinical management of HCC. Epithelial cell transforming sequence 2 (ECT2) has been implicated in human cancers, but its function in HCC is largely unknown.MethodsECT2 expression was studied by microarrays, immunoblotting and immunohistochemistry in human HCC samples. siRNA- and lentiviral vector-mediated knockdown were employed to decipher the molecular functions of ECT2.ResultsThe upregulation of ECT2 is significantly associated with early recurrent HCC disease and poor survival. Knockdown of ECT2 markedly suppressed Rho GTPases activities, enhanced apoptosis, attenuated oncogenicity and reduced the metastatic ability of HCC cells. Moreover, knockdown of ECT2 or Rho also suppressed ERK activation, while the silencing of Rho or ERK led to a marked reduction in cell migration. Stable knockdown of ECT2 in vivo resulted in significant retardation of tumour growth and the suppression of ERK activation. High expression of ECT2 correlates with high ERK phosphorylation and poor survival of HCC patients. Furthermore, ECT2 enhances the expression and stability of RACGAP1, accelerating ECT2-mediated Rho activation to promote metastasis.ConclusionsECT2 is closely associated with the activation of the Rho/ERK signalling axis to promote early HCC recurrence. In addition, ECT2 can crosstalk with RACGAP1 to catalyse the GTP exchange involved in Rho signalling to further regulate tumour initiation and metastasis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 62, Issue 6, June 2015, Pages 1287-1295
نویسندگان
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