Laboratory of Experimental Endocrinology, School of Medicine, University of Crete, 71003 Heraklion, Greece.
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
Cells. 2023 Feb 18;12(4):653. doi: 10.3390/cells12040653.
The estrogen receptor α (ERα) corresponds to a large platform in charge of the recruitment of a panel of molecules, including steroids and related heterocyclic derivatives, oligonucleotides, peptides and proteins. Its 295-311 region is particularly targeted by post-translational modifications, suggesting that it could be crucial for the control of transcription. In addition to anionic phospholipids, the ERα 295-311 fragment interacts with Ca-calmodulin, the heat shock protein 70 (Hsp70), ERα and possibly importins. More recently, we have demonstrated that it is prone to interacting with the G-protein-coupled estrogen receptor (GPER). In light of these observations, the pharmacological profile of the corresponding peptide, namely ERα17p, has been explored in breast cancer cells. Remarkably, it exerts apoptosis through GPER and induces a significant decrease (more than 50%) of the size of triple-negative breast tumor xenografts in mice. Herein, we highlight not only the promising therapeutic perspectives in the use of the first peptidic GPER modulator ERα17p, but also the opportunity to modulate GPER for clinical purposes.
雌激素受体 α（ERα）对应一个大型平台，负责招募一系列分子，包括甾体和相关杂环衍生物、寡核苷酸、肽和蛋白质。其 295-311 区域特别受到翻译后修饰的靶向作用，这表明它可能对转录控制至关重要。除了阴离子磷脂外，ERα 295-311 片段还与钙调蛋白、热休克蛋白 70（Hsp70）、ERα 和可能的导入蛋白相互作用。最近，我们已经证明它容易与 G 蛋白偶联雌激素受体（GPER）相互作用。鉴于这些观察结果，我们已经在乳腺癌细胞中探索了相应肽段（即 ERα17p）的药理学特性。值得注意的是，它通过 GPER 诱导细胞凋亡，并显著减少（超过 50%）三阴性乳腺癌肿瘤异种移植物在小鼠中的大小。在此，我们不仅强调了使用第一个肽类 GPER 调节剂 ERα17p 的有前途的治疗前景，还强调了为临床目的调节 GPER 的机会。
