Gab2通过GSK-3β/Snail信号通路促进乳腺癌的上皮-间质转化

doi:10.3969/j.issn.1007-3969.2016.02.003

中国癌症杂志 ›› 2016, Vol. 26 ›› Issue (2): 134-139.doi: 10.3969/j.issn.1007-3969.2016.02.003

Gab2通过GSK-3β/Snail信号通路促进乳腺癌的上皮-间质转化

田红艳¹，李　笑²，孙志亮²，李洪利³，刘雨清¹，尹崇高⁴

1. 潍坊医学院病理学教研室，山东潍坊 261053 ；
2. 潍坊医学院生物科学与技术学院，山东潍坊 261053 ；
3. 潍坊医学院医学研究实验中心，山东潍坊 261053 ；
4. 潍坊医学院护理学院，山东潍坊 261053

出版日期:2016-02-29 发布日期:2016-06-01
通信作者: 尹崇高　E-mail：lihongli1213@sina.com
基金资助:
国家自然科学基金青年基金项目(81402389)；山东省自然科学基金(ZR2014HL077)；山东省高等学校科技计划(J12LK03，J13LK03)；国家级大学生创新训练计划项目(201410438003)；潍坊医学院大学生科技创新基金(KX2014033)。

Gab2 promotes epithelial-mesenchymal transition in breast cancer through GSK-3β/Snail signaling pathway

TIAN Hongyan¹, LI Xiao², SUN Zhiliang², LI Hongli³, LIU Yuqing¹, YIN Chonggao⁴

1.Department of Pathology, Weifang Medical University, Weifang 261053, Shandong Province, China; 2.College of Biological Science and Technology, Weifang Medical University, Weifang 261053, Shandong Province, China; 3.Medicine Research Center, Weifang Medical University, Weifang 261053, Shandong Province, China; 4.College of Nursing, Weifang Medical University, Weifang 261053, Shandong Province, China

Published:2016-02-29 Online:2016-06-01
Contact: YIN Chonggao E-mail: lihongli1213@sina.com

摘要/Abstract

摘要： 背景与目的：越来越多的证据显示，Grb2协同结合蛋白2(Grb2 binding protein-2，Gab2)与肿瘤的侵袭转移相关，但Gab2与乳腺癌上皮-间质转化(epithelial-mesenchymal transition，EMT)的关系尚不清楚。本研究旨在探讨Gab2对乳腺癌EMT标志物的影响，明确Gab2在乳腺癌侵袭和转移中的作用机制。方法：采用免疫组织化学染色法检测80例乳腺癌组织中Gab2及EMT标记物上皮性钙黏着蛋白(E-cadherin)、波形蛋白(vimentin)的表达情况并分析其相关性，用蛋白［质］印迹法(Western blot)检测乳腺组织Gab2的表达情况，采用小干扰RNA(siRNA)技术降低乳腺癌细胞系MDA-MB-231中Gab2的表达，采用划痕实验检测表皮生长因子(epithelial growth factor，EGF)刺激后转染细胞的侵袭能力变化，用Western blot检测敲低Gab2后MDAMB-231细胞中E-cadherin及vimentin的表达情况，同时检测p-GSK-3β的表达情况、转录因子Snail转核情况。结果：Gab2在乳腺癌组织中的表达与E-cadherin的表达呈负相关，而与vimentin的表达呈正相关(P<0.05)；乳腺癌组织中Gab2的表达量明显高于正常乳腺组织；siRNA质粒转染后，SiGab2/MDA-MB-231细胞组中Gab2蛋白的表达量明显降低，结果显示转染成功，划痕实验显示细胞的侵袭能力减弱，表明Gab2影响乳腺癌细胞系的侵袭能力；敲低Gab2后，MDA-MB-231细胞中的E-cadherin的表达明显升高，而vimentin的表达明显降低；GSK-3β的磷酸化受到抑制，而Snail在敲低Gab2的细胞核中的表达明显下调。结论：Gab2可以通过GSK-3β/Snail信号通路促进乳腺癌的EMT，从而促进乳腺癌的侵袭和转移。

关键词: 乳腺癌, 侵袭, Grb2协同结合蛋白2, 上皮-间质转化, 信号通路

Abstract: Background and purpose: More and more evidence has showed that Grb2 binding protein-2 (Gab2) is associated with tumor invasion and metastasis. However, the relationship between Gab2 and epithelialmesenchymal transition (EMT) in breast cancer is not clear. The aim of this study is to investigate the effect of Gab2 on EMT markers and the mechanism of Gab2 on breast cancer invasion and metastasis. Methods: Immunohistochemical methods were used to detect the expressions of Gab2, E-cadherin and vimentin in 80 cases of breast cancer tissues, and the correlations between them were analyzed. Western blot was used to detect the expression of Gab2 in breast tissues. After MDA-MB-231 cells were transfected with siRNA plasmid, wound healing assay was used to detect the invasive ability of transfected cells induced by epithelial growth factor (EGF) in vitro. Then Western blot was used to analyze the protein expressions of E-cadherin, vimentin, phosphorylated GSK-3β (p-GSK-3β) and nuclear Snail. Results: Gab2 was negatively correlated with the expression of E-cadherin and positively correlated with the expression of vimentin in breast cancer tissues (P<0.05). The expression of Gab2 in breast cancer tissues was higher than that in normal breast tissues adjacent to breast cancer. In vitro, Gab2 expression was significantly knocked down in MDA-MB-231 cells transfected with Gab2 siRNA plasmid (SiGab2/MDA-MB-231cells). Meanwhile, the invasive ability of SiGab2/MDAMB-231cells was decreased with EGF stimulation. The expression of E-cadherin was increased in SiGab2/MDA-MB-231cells. However, the expressions of vimentin, p-GSK-3β and nuclear Snail were decreased in SiGab2/MDA-MB- 231cells. Conclusion: Gab2 can promote the invasion and metastasis of breast cancer by EMT through GSK-3β/Snail signaling pathway.

Key words: Breast cancer, Invasion, Grb2 binding protein-2, Epithelial-mesenchymal transition, Signaling pathway

田红艳,李　笑,孙志亮,等. Gab2通过GSK-3β/Snail信号通路促进乳腺癌的上皮-间质转化[J]. 中国癌症杂志, 2016, 26(2): 134-139.

TIAN Hongyan, LI Xiao, SUN Zhiliang, et al. Gab2 promotes epithelial-mesenchymal transition in breast cancer through GSK-3β/Snail signaling pathway[J]. China Oncology, 2016, 26(2): 134-139.

[1]	章箎, 陈佳慧, 林瑾仪, 王妍, 张斯加, 朱玮, 程蕾蕾. 一种新型《乳腺癌治疗相关心血管毒性临床评分表》的价值分析[J]. 中国癌症杂志, 2022, 32(1): 54-60.
[2]	金奕滋, 林明曦, 张剑. DNA损伤应答缺陷作为乳腺癌治疗靶点的研究进展[J]. 中国癌症杂志, 2022, 32(1): 61-67.
[3]	《中国乳腺癌新辅助治疗专家共识（2022年版）》专家组. 中国乳腺癌新辅助治疗专家共识（2022年版）[J]. 中国癌症杂志, 2022, 32(1): 80-89.
[4]	张小艳, 李清祥, 刘　勇, 李　航, 仇丽娟, 封欣然, 谭立明 . HMGB1与乳腺癌患者临床病理学特征及免疫指标的相关性研究[J]. 中国癌症杂志, 2021, 31(9): 783-788.
[5]	曹爱玲, 曹　喆, 周　剑. 多西他赛联合胸腺肽α1对大鼠乳腺癌免疫微环境中Treg数量的影响及其机制研究[J]. 中国癌症杂志, 2021, 31(9): 799-806.
[6]	姚　嘉, 李冠乔, 杨时平, 苏慧銮 . Hsa-miR-98-5p/DKK3信号轴对乳腺癌细胞生物学行为的影响[J]. 中国癌症杂志, 2021, 31(9): 807-816.
[7]	丛斌斌, 王永胜. 激素受体阳性早期乳腺癌治疗现状与挑战[J]. 中国癌症杂志, 2021, 31(8): 689-696.
[8]	杨士鹏, 刘颖, 王馨悦, 杨洋, 全吉淑, 林贞花 . PKLR在胰腺癌中的表达水平及临床病理学意义[J]. 中国癌症杂志, 2021, 31(8): 704-713.
[9]	张学成, 关晓辉 . Circ_0007142吸附miR-647调控CCR8基因促进胃癌细胞的上皮-间质转化和侵袭[J]. 中国癌症杂志, 2021, 31(8): 714-724.
[10]	朱逸晖, 李　婷, 胡夕春. Trastuzumab deruxtecan的临床研究进展及展望——HER2耐药患者的新希望[J]. 中国癌症杂志, 2021, 31(8): 754-761.
[11]	丁高峰, 郭雷鸣, 陆寓非. 乳腺癌患者HER2和BRCA1表达与放疗敏感性的关系研究[J]. 中国癌症杂志, 2021, 31(7): 589-595.
[12]	金优萍, 李录英, 周　平. 长链非编码RNA STMN1P2在乳腺癌中的作用及机制研究[J]. 中国癌症杂志, 2021, 31(7): 596-604.
[13]	谢金芳, 曹春雨, 任　雪, 田家俊, 吕亚丰, 黄晓飞 . 萝卜硫素对小鼠乳腺癌4T1细胞上皮-间质转化、增殖和迁移的影响研究[J]. 中国癌症杂志, 2021, 31(7): 605-615.
[14]	曹达龙, 朱文恺, 施国海, 张海梁, 王子良, 叶定伟. PRUNE2点突变影响前列腺癌DU145细胞增殖、凋亡、侵袭和迁移[J]. 中国癌症杂志, 2021, 31(6): 441-446.
[15]	胡雅琼, 白　俊, 陈　琳, 陈新璐, 张丽萍, 周丹丹, 王　玉, 尹崇高, 李洪利, 刘雨清 . miR-625-5p通过靶向调控PRKACA促进肺腺癌细胞的增殖和侵袭[J]. 中国癌症杂志, 2021, 31(6): 447-454.

Gab2通过GSK-3β/Snail信号通路促进乳腺癌的上皮-间质转化

Gab2 promotes epithelial-mesenchymal transition in breast cancer through GSK-3β/Snail signaling pathway

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价