The Clinical Medical Research Center of Breast and Thyroid Tumor in Xinjiang, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi City, Xinjiang Uygur Autonomous Region 830011, China.
The Clinical Medical Research Center of Breast and Thyroid Tumor in Xinjiang, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi City, Xinjiang Uygur Autonomous Region 830011, China.
Tissue Cell. 2024 Aug;89:102455. doi: 10.1016/j.tice.2024.102455. Epub 2024 Jun 21.
Breast cancer (BC) is the most common type of fatal cancer in women. New therapeutic strategies need to be explored to enhance the efficacy of doxorubicin by overcoming the resistance of BC cells. NUF2 is a component of the Ndc80 centromere complex and is a key substance in mediating mitosis and affects the progression of multiple tumors. However, the role as well as mechanisms of NUF2 resistance in BC remain unclear. This study aims to reveal the role of NUF2 in drug resistance in BC. We here revealed that NUF2 was highly expressed in human BC. NUF2 depletion-derived exosomes blocked the growth of BC cells. Further, NUF2 ablation-derived exosomes inhibited autophagy in BC cells. Also, NUF2 ablation-derived exosomes improved doxorubicin resistance in BC cells. Mechanically, NUF2 ablation-derived exosomes blocked PI3K/AKT/mTOR axis in BC cells. In summary, NUF2 ablation-derived exosomes blocked the autophagy of BC cells and improved doxorubicin resistance via mediating PI3K/AKT/mTOR axis.
乳腺癌（BC）是女性最常见的致命癌症类型。需要探索新的治疗策略，通过克服 BC 细胞的耐药性来提高多柔比星的疗效。NUF2 是 Ndc80 着丝粒复合物的一个组成部分，是介导有丝分裂的关键物质，影响多种肿瘤的进展。然而，NUF2 在 BC 中的耐药作用及其机制尚不清楚。本研究旨在揭示 NUF2 在 BC 耐药中的作用。我们在这里揭示 NUF2 在人乳腺癌中高表达。NUF2 耗竭衍生的外体阻断了 BC 细胞的生长。此外，NUF2 缺失衍生的外体抑制了 BC 细胞的自噬。此外，NUF2 缺失衍生的外体提高了 BC 细胞对多柔比星的耐药性。从机制上讲，NUF2 缺失衍生的外体通过阻断 BC 细胞中的 PI3K/AKT/mTOR 轴来发挥作用。总之，NUF2 缺失衍生的外体通过介导 PI3K/AKT/mTOR 轴阻断 BC 细胞的自噬并提高多柔比星耐药性。
Eur Rev Med Pharmacol Sci. 2018-5
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