Interaction of HE4 and ANXA2 exists in various malignant cells-HE4-ANXA2-MMP2 protein complex promotes cell migration

HE4与ANXA2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

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作者:Jing Wang #, Lu Deng #, Huiyu Zhuang, Juanjuan Liu, Dawo Liu, Xiao Li, Shan Jin, Liancheng Zhu, Huimin Wang, Bei Lin

Background

The 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.

Conclusions

The 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.

Methods

Real-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.

Results

Here 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. Conclusions: The 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.

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