Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT.

Yao Zhao, Chenchen Cai, Miaomiao Zhang, Lubing Shi, Jiwei Wang, Haoliang Zhang, Ping Ma, Shibao Li

Journal of cancer research and clinical oncology 2021 Jul

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Ephrin-A2, a member of the Eph receptor subgroup, is used in diagnosing and determining the prognosis of prostate cancer. However, the role of ephrin-A2 in prostate cancer is remains elusive. We established stable clones overexpressing or silencing ephrin-A2 from prostate cancer cells. Then, CCK-8 was used in analyzing the proliferation ability of cells. CD31 staining was used in evaluating angiogenesis. Migration and invasion assay were conducted in vivo and in vitro. The expression of EMT-related markers was evaluated in prostate cancer cells through Western blotting. We revealed that the ectopic expression of ephrin-A2 in prostate cancer cells facilitated cell migration and invasion in vitro and promoted tumor metastasis and angiogenesis in vivo and that the silencing of ephrin-A2 completely reversed this effect. Although ephrin-A2 did not affect tumor cell proliferation in vitro, ephrin-A2 significantly promoted primary tumor growth in vivo. Furthermore, to determine the biological function of ephrin-A2, we assayed the expression of EMT-related markers in stable-established cell lines. Results showed that the overexpression of ephrin-A2 in prostate cancer cells down-regulated the expression of epithelial markers (ZO-1, E-cadherin, and claudin-1) and up-regulated the expression of mesenchymal markers (N-cadherin, β-catenin, vimentin, Slug, and Snail), but the knocking out of ephrin-A2 opposed the effects on the expression of EMT markers. These findings indicate that ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT and may be a potentially therapeutic target in metastatic prostate cancer.

Citation

Yao Zhao, Chenchen Cai, Miaomiao Zhang, Lubing Shi, Jiwei Wang, Haoliang Zhang, Ping Ma, Shibao Li. Ephrin-A2 promotes prostate cancer metastasis by enhancing angiogenesis and promoting EMT. Journal of cancer research and clinical oncology. 2021 Jul;147(7):2013-2023