Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy.
FEBS Lett. 2011 Oct 20;585(20):3328-36. doi: 10.1016/j.febslet.2011.09.023. Epub 2011 Sep 28.
Increased expression of thioredoxin (Trx)-1 and matrix metalloproteinase (MMP)-9 associates with malignant breast cancer progression. Here, we describe a functional relationship between Trx-1 and MMP-9 in promoting MDA-MB-231 breast cancer cell invasive behaviour. Trx-1 overexpression stimulated MMP-9 expression, de-regulated the MMP-9/TIMP-1 equilibrium and augmented MMP-9 involvement in a more invasive phenotype. Trx-1 augmented MMP-9 transcription through NF-κB, AP-1 and SP1 elements; stimulated p50/p65 NF-κB activity and recruitment to the MMP-9 promoter; and facilitated MMP-9 promoter-accessibility to NF-κB by preventing HDAC recruitment and maintaining MMP-9 promoter histone acetylation. Our data provide a functional basis for Trx-1 and MMP-9 association in malignant breast cancer and identify Trx-1 and NF-κB as potentially druggable targets for reducing MMP-9 involvement in malignant behaviour.
硫氧还蛋白 (Trx)-1 和基质金属蛋白酶 (MMP)-9 的表达增加与乳腺癌的恶性进展有关。在这里，我们描述了 Trx-1 和 MMP-9 之间在促进 MDA-MB-231 乳腺癌细胞侵袭行为方面的功能关系。Trx-1 的过表达刺激了 MMP-9 的表达，使 MMP-9/TIMP-1 平衡失调，并增强了 MMP-9 参与更具侵袭性表型的能力。Trx-1 通过 NF-κB、AP-1 和 SP1 元件增强 MMP-9 的转录；刺激 p50/p65 NF-κB 活性和募集到 MMP-9 启动子；并通过防止 HDAC 募集和维持 MMP-9 启动子组蛋白乙酰化，促进 NF-κB 对 MMP-9 启动子的可及性。我们的数据为 Trx-1 和 MMP-9 在恶性乳腺癌中的关联提供了功能基础，并确定 Trx-1 和 NF-κB 是减少 MMP-9 参与恶性行为的潜在可用药靶点。
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