Interaction of HE4 and ANXA2 exists in various malignant cellsHE4-ANXA2-MMP2 protein complex promotes cell migration
Interaction of HE4 and ANXA2 exists in various malignant cellsHE4-ANXA2-MMP2 protein complex promotes cell migration
复制标题
HE4与ANXA2的相互作用存在于多种恶性细胞中——HE4-ANXA2-MMP2蛋白复合物促进细胞迁移
DOI：
10.1186/s12935-019-0864-4
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发表时间：
2019
影响因子：
5.8
通讯作者：
Lin Bei
中科院分区：
文献类型：
--
作者：
Wang Jing;Deng Lu;Zhuang Huiyu;Liu Juanjuan;Liu Dawo;Li Xiao;Jin Shan;Zhu Liancheng;Wang Huimin;Lin Bei
背景人附睾蛋白4（HE4）和膜联蛋白A2（Annexin A2）之间的相互作用已在卵巢癌中被发现。但在其他恶性肿瘤中是否存在这种相互作用尚不明确。方法采用实时荧光定量PCR、Western blotting和免疫细胞化学检测mRNA和蛋白的表达。采用免疫共沉淀和双标免疫荧光检测HE4、ANXA2和MMP2之间的相互作用。 MTS测定用于测试细胞增殖。粘附测试用于测试细胞粘附。应用流式细胞术检查细胞周期。通过划痕实验和Transwell实验检测各种恶性细胞系的迁移和侵袭能力。结果我们发现HE4和ANXA2在各种恶性细胞中的过表达是一种常见现象。 HE4和ANXA2共定位于多种肿瘤细胞的细胞质和细胞膜中。同时高表达HE4和ANXA2的ES-2细胞的增殖、粘附、侵袭和迁移能力均强于其他肿瘤细胞。 HE4-ANXA2-MMP2可以形成三重蛋白质复合物。 HE4可通过ANXA2介导MMP2的表达，促进细胞迁移进程。结论HE4与ANXA2的相互作用存在于多种类型的癌细胞中。 HE4和ANXA2可以促进癌细胞的增殖、粘附、侵袭和迁移。 HE4-ANXA2-MMP2形成蛋白复合物，ANXA2起到“桥梁”的作用。他们一起发挥作用来促进细胞迁移。
BackgroundThe interaction between human epididymis protein 4 (HE4) and annexin A2 (Annexin A2) has been found in ovarian cancer. However, it is dimness whether the interaction exists in other malignant tumors.MethodsReal-time PCR, western blotting and immunocytochemistry were used to detect mRNA and proteins expression. Co-immunoprecipitation and double-labeling immunofluorescence were used to detect the interaction among HE4, ANXA2 and MMP2. MTS assay was used to test cell proliferation. Adhesion test was used to test cell adhesion. Flow cytometry was applied to examine cell cycle. The scratch test and Transwell assay was performed to detect the migration and invasion of various malignant cell lines.ResultsHere we show that the overexpression of HE4 and ANXA2 in various malignant cells is a common phenomenon. HE4 and ANXA2 are co-localized in the cytoplasm and membrane of various tumor cells. ES-2 cells which had both high expression of HE4 and ANXA2 were much stronger in proliferation, adhesion, invasion, and migration than other tumor cells. HE4–ANXA2–MMP2 could form a triple protein complex. HE4 could mediate the expression of MMP2 via ANXA2 to promote cell migration progress.ConclusionsThe interaction of HE4 and ANXA2 exists in various types of cancer cells. HE4 and ANXA2 can promote the proliferation, adhesion, invasion, and migration of cancer cells. HE4–ANXA2–MMP2 form a protein complex and ANXA2 plays the role of “bridge”. They performed together to promote cell migration.