Stem Cells and Regenerative Medicine Branch, Egypt Center for Research and Regenerative Medicine (ECRRM), Cairo, Egypt.
Microbial Genetics Department, Biotechnology Research Institute, National Research Centre, Cairo, Egypt.
Sci Rep. 2024 Oct 4;14(1):23146. doi: 10.1038/s41598-024-71522-z.
Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptors and has a poor prognosis as it is resistant to chemotherapy. A new treatment option for this type of cancer may be by putting these malignant cells into dormancy. The oocyte's embryonic milieu presents a unique tumor reversion microenvironment by inducing growth arrest and changing cells' phenotypes. We conducted an in-silico study to determine the most likely oocyte extract (OE) proteins involved in inducing dormancy using HDock, CluPro, and molecular dynamic (MD) simulation. Results showed low energy scores for complexes between OE proteins and four surface markers: K1C14, CLD3, CLD4, and ITA6. Apolipoprotein A1 (APOA1) and Apolipoprotein C3 (APOC3) showed the highest stability and affinity with these four surface markers: K1C14, CLD3, CLD4, and ITA6. These proteins are involved in key tumor-related pathways such as angiogenesis, proliferation, apoptosis, and migration. This will pave the way for exploring novel therapeutic options to induce dormancy in TNBC cells.
三阴性乳腺癌(TNBC)缺乏雌激素、孕激素和人表皮生长因子受体,且对化疗有抗性,因此预后较差。通过使这些恶性细胞进入休眠状态,可能为这种类型的癌症提供一种新的治疗选择。卵母细胞的胚胎环境通过诱导生长停滞和改变细胞表型,提供了一个独特的肿瘤逆转微环境。我们使用 HDock、CluPro 和分子动力学 (MD) 模拟进行了一项计算机模拟研究,以确定最有可能参与诱导休眠的卵母细胞提取物 (OE) 蛋白。结果表明,OE 蛋白与四个表面标志物(K1C14、CLD3、CLD4 和 ITA6)之间的复合物具有较低的能量评分。载脂蛋白 A1 (APOA1) 和载脂蛋白 C3 (APOC3) 与这四个表面标志物(K1C14、CLD3、CLD4 和 ITA6)表现出最高的稳定性和亲和力。这些蛋白参与关键的肿瘤相关途径,如血管生成、增殖、凋亡和迁移。这将为探索诱导 TNBC 细胞休眠的新治疗选择铺平道路。