Diaphanous-related formin-3 overexpression inhibits the migration and invasion of triple-negative breast cancer by inhibiting RhoA-GTP expression
Diaphanous-related formin-3 overexpression inhibits the migration and invasion of triple-negative breast cancer by inhibiting RhoA-GTP expression
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DOI：
10.1016/j.biopha.2017.07.119
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发表时间：
2017-10-01
影响因子：
7.5
通讯作者：
Jiang, Jinyan
中科院分区：
文献类型：
--
作者：
Jiang, Jinyan
三阴性乳腺癌（TNBC）与转移、复发和预后不良的高风险相关。TNBC对现有的内分泌和靶向乳腺癌疗法不敏感，因为它缺乏雌激素受体、孕酮受体和人表皮生长因子受体2的表达。因此，迫切需要鉴定新的靶标以提高TNBC治疗的功效。透明相关的β-淀粉样蛋白-3（DIAPH 3）调节细胞骨架的形成以调节细胞粘附、迁移和分化。先前的研究表明DIAPH 3促进前列腺癌的转移。然而，DIAPH 3在TNBC中的表达及其对TNBC发展的影响迄今尚未报道。本研究旨在探讨DIAPH 3在TNBC中的表达及功能。免疫组化染色结果显示DIAPH 3在乳腺癌组织中的表达明显低于配对的非肿瘤组织，尤其是TNBC组织。此外，DIAPH 3表达与TNM分期和淋巴结转移有关，但与TNBC患者的肿瘤大小无关。此外，DIAPH 3过表达明显抑制MDA-MB-231细胞的迁移和侵袭，并降低Ras同源家族成员A（RhoA）、RhoA-GTP、基质金属肽酶2（MMP-2）和MMP-9的表达。因此，我们预测DIAPH 3过表达通过抑制RhoA-GTP表达来抑制TNBC的迁移和侵袭，并且本研究的结果为开发针对TNBC的DIAPH 3靶向疗法提供了新的见解。(C)2017年由Elsevier Masson SAS出版。
Triple-negative breast cancer (TNBC) is associated with a high risk of metastasis, recurrence, and poor prognosis. TNBC is insensitive to existing endocrine and targeted breast cancer therapies because it lacks the expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Therefore, there is an urgent need for identifying novel targets to improve the efficacy of TNBC treatment. Diaphanous-related formin-3 (DIAPH3) regulates cytoskeleton formation to regulate cell adhesion, migration, and differentiation. A previous study showed that DIAPH3 promoted the metastasis of prostate cancer. However, DIAPH3 expression in TNBC and its effect on TNBC development have not been reported to date. In present study, we investigated the expression and functions of DIAPH3 in TNBC. Results of immunohistochemical staining showed that DIAPH3 expression significantly decreased in breast cancer tissues, especially TNBC tissues, compared with that in paired non-tumor tissues. In addition, DIAPH3 expression was associated with TNM stage and lymph node metastasis, but not with tumor size in patients with TNBC. Further, DIAPH3 overexpression clearly suppressed the migration and invasion of MDA-MB-231 cells and decreased the expression of Ras Homolog Family Member A (RhoA), RhoA-GTP, Matrix Metallopeptidase 2 (MMP-2), and MMP-9. Thus, we predict that DIAPH3 overexpression inhibits the migration and invasion of TNBC by inhibiting RhoA-GTP expression and the results of the present study provide new insights for developing DIAPH3-targeting therapies for TNBC. (C) 2017 Published by Elsevier Masson SAS.