College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, Gwangju 61186, Korea.
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon 57922, Korea.
Int J Mol Sci. 2021 May 18;22(10):5306. doi: 10.3390/ijms22105306.
Prostate cancer (PCa) is the second most leading cause of death in males. Our previous studies have demonstrated that δ-catenin plays an important role in prostate cancer progression. However, the molecular mechanism underlying the regulation of δ-catenin has not been fully explored yet. In the present study, we found that δ-catenin could induce phosphorylation of p21 and stabilize p21 in the cytoplasm, thus blocking its nuclear accumulation for the first time. We also found that δ-catenin could regulate the interaction between AKT and p21, leading to phosphorylation of p21 at Thr-145 residue. Finally, EGF was found to be a key factor upstream of AKT/δ-catenin/p21 for promoting proliferation and metastasis in prostate cancer. Our findings provide new insights into molecular controls of EGF and the development of potential therapeutics targeting δ-catenin to control prostate cancer progression.
前列腺癌(PCa)是男性死亡的第二大主要原因。我们之前的研究表明,δ-连环蛋白在前列腺癌的进展中起着重要作用。然而,其调控的分子机制尚未被完全探索。在本研究中,我们首次发现δ-连环蛋白可以诱导 p21 的磷酸化,并将其稳定在细胞质中,从而阻止其核内积累。我们还发现,δ-连环蛋白可以调节 AKT 和 p21 之间的相互作用,导致 p21 在 Thr-145 残基上的磷酸化。最后,发现表皮生长因子(EGF)是 AKT/δ-连环蛋白/p21 促进前列腺癌增殖和转移的上游关键因素。我们的研究结果为 EGF 的分子调控以及开发针对δ-连环蛋白的潜在治疗方法以控制前列腺癌的进展提供了新的见解。