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RHAMM 通过 AKT/GSK3β/Snail 轴抑制腔 A 型乳腺癌细胞迁移。

RHAMM inhibits cell migration via the AKT/GSK3β/Snail axis in luminal A subtype breast cancer.

机构信息

Department of Anatomy and Histology, School of Medicine, Nankai University, Tianjin, China.

Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, China.

出版信息

Anat Rec (Hoboken). 2020 Sep;303(9):2344-2356. doi: 10.1002/ar.24321. Epub 2019 Dec 10.

Abstract

Breast cancer is one of the most common types of cancer in women. Although the mortality rate of breast cancer has fallen over the past 10 years, effective treatments that reduce the occurrence of breast cancer metastasis remain lacking. In this study, we explored the role of receptor for hyaluronan mediated motility (RHAMM) and the associated signaling pathway in cell migration in luminal A breast cancer. We first examined RHAMM expression levels using human breast tissue microarray and patient breast tissues. We then studied the role of RHAMM in migration in luminal A breast cancer using loss-of-function and gain-of-function strategies in in vitro models and confirmed these findings in an in vivo model. Finally, we investigated signaling molecules that play a role in cell migration using western blot. Our results demonstrated the following: (a) RHAMM shows high expression levels in malignant breast tissue, (b) RHAMM shows low expression levels in luminal A breast cancer compared to other subtypes of breast cancer, (c) RHAMM inhibits cell migration in luminal A breast cancer, and (d) RHAMM inhibits cell migration via the AKT/GSK3β/Snail axis in luminal A breast cancer. This study demonstrates a novel role of RHAMM in cell migration in luminal A breast cancer and suggests that therapeutic strategies involving RHAMM should be considered for various subtypes of breast cancer.

摘要

乳腺癌是女性最常见的癌症类型之一。尽管过去 10 年来乳腺癌的死亡率有所下降,但缺乏能够减少乳腺癌转移发生的有效治疗方法。在这项研究中,我们探讨了透明质酸介导的运动受体 (RHAMM) 及其相关信号通路在腔 A 型乳腺癌细胞迁移中的作用。我们首先使用人乳腺癌组织微阵列和患者乳腺癌组织检测 RHAMM 表达水平。然后,我们在体外模型中使用功能丧失和功能获得策略研究 RHAMM 在腔 A 型乳腺癌迁移中的作用,并在体内模型中证实了这些发现。最后,我们使用 Western blot 研究了在细胞迁移中起作用的信号分子。我们的结果表明:(a) RHAMM 在恶性乳腺组织中表达水平较高;(b) RHAMM 在腔 A 型乳腺癌中的表达水平低于其他乳腺癌亚型;(c) RHAMM 抑制腔 A 型乳腺癌细胞迁移;(d) RHAMM 通过 AKT/GSK3β/Snail 轴抑制腔 A 型乳腺癌细胞迁移。这项研究表明 RHAMM 在腔 A 型乳腺癌细胞迁移中具有新的作用,并提示针对不同乳腺癌亚型应考虑涉及 RHAMM 的治疗策略。

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