Overexpression of GATA5 Inhibits Prostate Cancer Progression by Regulating PLAGL2 via the FAK/PI3K/AKT Pathway

SIMPLE SUMMARY: Prostate cancer (PCa) has the highest incidence of malignant tumors and is the second-ranked tumor-causing death of men. GATA binding protein 5 (GATA5) belongs to the GATA gene family and we found that GATA5 was downregulated in PCa tissues, but the function of GATA5 in PCa remains elusive. We found overexpression GATA5 inhibited tumor proliferation, migration, invasion and the process of epithelial–mesenchymal transition (EMT), and upregulation of GATA5 promoted PCa cell apoptosis. In addition, we disclosed that GATA5 could interact with pleomorphic adenoma gene-like-2 (PLAGL2) to regulate PCa cell growth via FAK/PI3K/AKT signaling pathway. Hence, these findings suggested that GATA5 could serve as a new therapeutic target in the future. ABSTRACT: Background: Prostate cancer (PCa) is a malignancy with high incidence and the principal cause of cancer deaths in men. GATA binding protein 5 (GATA5) belongs to the GATA gene family. GATA5 has a close association with carcinogenesis, but the role of GATA5 in PCa remains poorly understood. The aim of our present study was to probe into the effect of GATA5 on PCa progression and to elucidate the involved mechanism. Methods: The expression of GATA5 was detected in both PCa samples and PCa cell lines. GATA5 overexpression, PLAGL2 knockdown, and overexpression cell models were generated, then Western blotting experiments were utilized to validate the efficiency of transfection. The effects of GATA5 on PCa cell proliferation, metastasis, apoptosis, cell cycle progression, and EMT were detected in vitro or in vivo. Furthermore, the mechanism by which GATA5 inhibits prostate cancer progression through regulating PLAGL2 via the FAK/PI3K/AKT pathway was also explored. Results: GATA5 expression was downregulated in PCa samples and cell lines. GATA5 overexpression inhibited PCa cell proliferation and metastasis but increased the rate of apoptosis. In addition, we confirmed that GATA5 inhibited prostate cancer progression, including EMT, by regulating PLAGL2 via the FAK/PI3K/AKT pathway. Conclusion: We demonstrated that GATA5, as a tumor suppressor in PCa, inhibits PCa progression by regulating PLAGL2. These results showed that the GATA5/PLAGL2/FAK/PI3K/AKT pathway may become a new therapeutic direction for the treatment of PCa.