Human Sprouty1 suppresses growth, migration, and invasion in human breast cancer cells

被引:16
作者
Mekkawy, Ahmed H. [1 ]
Pourgholami, Mohammad H. [1 ]
Morris, David L. [1 ,2 ]
机构
[1] Univ New S Wales, Dept Surg, Canc Res Labs, Sydney, NSW 2217, Australia
[2] Univ New S Wales, Dept Surg, St George Hosp, Sydney, NSW 2217, Australia
关键词
Breast cancer; Sprouty; Proliferation; Adhesion; Migration; Invasion; VEGF; ERK ACTIVATION; ANGIOGENESIS; INHIBITOR; VEGF; RECEPTOR; DIFFERENTIATION; EXPRESSION; PROTEINS; PATHWAY;
D O I
10.1007/s13277-014-1665-y
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer is the most common cancer and the leading cause of cancer death in women worldwide. Expression of human Sprouty1 (hSpry1) gene is downregulated in most breast cancer patients, implicating it as an important tumor suppressor gene. So, we hypothesized that overexpression of hSpry1 gene may suppress breast cancer cell growth, migration, and invasion. Here, we demonstrate that in breast cancer cell lines, MDA-MB-231 and T47D, transfection-induced overexpression of hSpry1 reduced cell population, proliferation, and colony formation in vitro without affecting cell apoptosis. Adhesion molecules act as both positive and negative modulators of cellular migration and invasion. Here, we found that overexpression of hSpry1 enhances the initial establishment events in breast cancer cell adhesion to type IV collagen and vitronectin. Moreover, the overexpression of hSpry1 in the highly invasive MDA-MB-231 breast cancer cells causes a significant reduction in cellular migration and invasion through Matrigel membranes. In addition, we showed that hSpry1 overexpression prevents VEGF secretion. VEGF is essential for primary tumor growth, migration, and invasion. Thus, our study provides a novel mechanism of tumor suppression activity of hSpry1.
引用
收藏
页码:5037 / 5048
页数:12
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