کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2831100 | 1570726 | 2013 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Downregulation of Erbin in Her2-overexpressing breast cancer cells promotes cell migration and induces trastuzumab resistance Downregulation of Erbin in Her2-overexpressing breast cancer cells promotes cell migration and induces trastuzumab resistance](/preview/png/2831100.png)
• Erbin is significantly downregulated or lost in breast cancer tissues.
• Erbin deficiency results in an enhancement in heregulin-induced AKT activation.
• Knockdown of Erbin promotes cell migration, induces invasive phenotype of breast cancer cells and antagonizes the antiproliferative effect of trastuzumab.
• Erbin is a negative regulator of AKT activation.
Erbin is ubiquitously expressed in normal epithelial tissues and constitutively associates with Her2 at the basolateral membranes in epithelial cells. The inhibitory role of Erbin in ERK signaling has been demonstrated. However, whether the expression of Erbin is altered in Her2-overexpressing breast cancer is unclear. There is little information regarding the function of Erbin in cancer progression. In the present study, we demonstrate that the level of Erbin is significantly downregulated or lost in breast cancer tissues. Erbin deficiency resulted in a dramatic enhancement in heregulin-induced AKT activation and overexpression of Erbin not only significantly decreased the intensity of heregulin-induced AKT phosphorylation but also shortened its duration in Her2-overexpressing breast cancer cells. Knockdown of Erbin remarkably promotes cell migration, induces invasive phenotype of breast cancer cells and antagonized the anti-proliferative effect of therapeutic antibody trastuzumab. Treatment with AKT inhibitor GDC0941 dramatically reversed the effects of Erbin knockdown on the cell migration and trastuzumab resistance, which is mainly mediated by aberrant activation of AKT. The data reveal that Erbin is a negative regulator of AKT activation and suggest that Erbin may play a role in breast cancer progression.
Journal: Molecular Immunology - Volume 56, Issues 1–2, November 2013, Pages 104–112