Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio 7, 80138 Naples, Italy.
Department of Translational Medical Science, University of Naples "Federico II", Via S. Pansini 5, 80131 Naples, Italy.
Cells. 2021 Dec 22;11(1):14. doi: 10.3390/cells11010014.
Prostate cancer (PC) is one of the most widespread malignancies among males worldwide. The androgen receptor (AR) plays a major role in prostate cancer development and progression and is the main target of PC therapy. Nonetheless, its action is not yet fully elucidated. We report here that the AR associates with Filamin A (FlnA) promoting migration and invasiveness of various PC-derived cells after androgen challenging. Inhibition of the AR/FlnA complex assembly by a very low concentration of Rh-2025u, an AR-derived peptide specifically interfering with this association, impairs such phenotype in monolayer cells and in 3D models. This study, together with our recent data in cancer-associated fibroblasts (CAFs), indicates that targeting the AR/FlnA complex could improve the clinical management of invasive PC, as the limited number of new drugs reaching the market suggests that we must re-examine the way invasive PC is currently treated. In this context, the synthesis of new biologically active molecules, such as the Rh-2025u peptide, which has been shown to efficiently interfere in the complex assembly in CAFs and PC cells, should overcome the limits of current available therapies, mostly based on hormone antagonists.
前列腺癌（PC）是全球男性中最常见的恶性肿瘤之一。雄激素受体（AR）在前列腺癌的发生和发展中起主要作用，是前列腺癌治疗的主要靶点。然而，其作用尚未完全阐明。我们在这里报告，AR 与细丝蛋白 A（FlnA）结合，在雄激素刺激后促进各种前列腺癌细胞的迁移和侵袭。用非常低浓度的 Rh-2025u（一种 AR 衍生肽，专门干扰这种结合）抑制 AR/FlnA 复合物的组装，会损害单层细胞和 3D 模型中的这种表型。这项研究，以及我们最近在癌症相关成纤维细胞（CAFs）中的数据表明，靶向 AR/FlnA 复合物可能改善侵袭性前列腺癌的临床管理，因为进入市场的新药数量有限，这表明我们必须重新审视目前治疗侵袭性前列腺癌的方法。在这种情况下，合成新的生物活性分子，如 Rh-2025u 肽，已被证明能有效地干扰 CAFs 和 PC 细胞中复合物的组装，应克服当前可用疗法的局限性，这些疗法主要基于激素拮抗剂。
