Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, 475000, China.
Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, 475000, China.
Chem Biol Interact. 2020 Feb 1;317:108960. doi: 10.1016/j.cbi.2020.108960. Epub 2020 Jan 22.
Tripartite motif (TRIM) protein family is a group of proteins, which belongs to RING family of ubiquitin E3 ligases. TRIM proteins are involved in oncogenesis, while the roles in different cancers are controversial. However, the expression pattern and biological functions of TRIM47 in breast cancer remain unclear. In the present study, we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer. TRIM47 was found to be significantly up-regulated in breast cancer tissues and cell lines. TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation, migration, and invasion. Besides, TRIM47 knockdown regulated the expressions of the epithelial-mesenchymal transition (EMT)-related markers including increase in E-cadherin, and decrease in N-cadherin, vimentin and Snail. Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth in vivo. Furthermore, TRIM47 knockdown markedly inhibited the activation of PI3K/Akt signaling pathway, while the effects of TRIM47 knockdown were reversed by the treatment of insulin-like growth factor-1 (IGF-1), which is an activator of PI3K/Akt. Taken together, the findings indicated that knockdown of TRIM47 suppressed tumorigenesis and progression of breast cancer through the inhibition of PI3K/Akt pathway, and suggested that TRIM47 might be a potential therapy target for breast cancer treatment.
三结构域蛋白（TRIM）家族是一组蛋白，属于泛素 E3 连接酶的 RING 家族。TRIM 蛋白参与肿瘤发生，而在不同癌症中的作用存在争议。然而，TRIM47 在乳腺癌中的表达模式和生物学功能仍不清楚。在本研究中，我们旨在研究 TRIM47 在乳腺癌进展和转移中的作用。研究发现，TRIM47 在乳腺癌组织和细胞系中显著上调。在乳腺癌细胞系中敲低 TRIM47 显著抑制细胞增殖、迁移和侵袭。此外，TRIM47 敲低调节上皮-间充质转化（EMT）相关标志物的表达，包括 E-钙黏蛋白增加，N-钙黏蛋白、波形蛋白和 SNAIL 减少。异种移植肿瘤实验证明，TRIM47 敲低也抑制了体内肿瘤的生长。此外，TRIM47 敲低显著抑制了 PI3K/Akt 信号通路的激活，而 TRIM47 敲低的作用可被胰岛素样生长因子-1（IGF-1）逆转，IGF-1 是 PI3K/Akt 的激活剂。总之，这些发现表明，敲低 TRIM47 通过抑制 PI3K/Akt 通路抑制乳腺癌的发生和进展，提示 TRIM47 可能是乳腺癌治疗的潜在治疗靶点。
