Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies.

中文翻译：

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转化生长因子 β 活化激酶 1 抑制剂通过 TGF-β/TGFR 通路抑制三阴性乳腺癌的增殖。

乳腺癌是女性人群中最具侵袭性的癌症类型之一。转化生长因子β活化激酶1（TAK1）在乳腺癌进展中的功能活性越来越受到关注，因为它为抗乳腺癌药物开发提供了潜在的靶点。然而，TAK1 在三阴性乳腺癌 (TNBC) 进展中的基本作用以及潜在的抗 TAK1 候选药物的作用需要进一步评估。在这里，我们专注于 TAK1 在人类乳腺癌细胞中的作用，我们假设 TAK1 活化的抑制可以抑制人类 TNBC 细胞的生长。我们发现 TAK1 在临床来源的 TNBC 样本的癌细胞群和培养的人乳腺癌细胞系中被强烈激活。此外，我们确定了 TAK1 特异性小分子抑制剂 5Z-7-oxozaeenol (5Z-O) 对人 TNBC 细胞系增殖的影响。5Z-O 处理显着抑制了人 TNBC 细胞的增殖。总的来说，这些证明了 TAK1 在人类乳腺癌中的作用和 TAK1 抑制剂的抗增殖作用。我们的研究为进一步研究 TAK1 作为开发抗 TNBC 药物和治疗策略的有希望的靶点奠定了基础。