Zhang Ying, Lu Qian, Li Nan, Xu Ming, Miyamoto Tatsuo, Liu Jing
Department of Molecular and Cellular Physiology, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University, Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505, Japan.
NPJ Breast Cancer. 2022 Mar 24;8(1):40. doi: 10.1038/s41523-022-00402-4.
Breast cancer metastasis is the main cause of cancer death in women, so far, no effective treatment has inhibited breast cancer metastasis. Sulforaphane (SFN), a natural compound derived from broccoli, has shown potential health benefits in many cancers. However, research on breast cancer metastasis is still insufficient. Here, we showed that SFN, including its two isomers of R-SFN and S-SFN, significantly inhibited TGF-β1-induced migration and invasion in breast cancer cells. Proteomic and phosphoproteomic analysis showed that SFN affected the formation of the cytoskeleton. Subsequent experiments confirmed that SFN significantly inhibited TGF-β1-induced actin stress fiber formation and the expression of actin stress fiber formation-associated proteins, including paxillin, IQGAP1, FAK, PAK2, and ROCK. Additionally, SFN is directly bound to RAF family proteins (including ARAF, BRAF, and CRAF) and inhibited MEK and ERK phosphorylation. These in vitro results indicate that SFN targets the RAF/MEK/ERK signaling pathway to inhibit the formation of actin stress fibers, thereby inhibiting breast cancer cell metastasis.
乳腺癌转移是女性癌症死亡的主要原因，迄今为止，尚无有效的治疗方法能抑制乳腺癌转移。萝卜硫素（SFN）是一种从西兰花中提取的天然化合物，在许多癌症中都显示出潜在的健康益处。然而，关于乳腺癌转移的研究仍然不足。在此，我们表明，SFN，包括其两种异构体R-SFN和S-SFN，显著抑制了TGF-β1诱导的乳腺癌细胞迁移和侵袭。蛋白质组学和磷酸化蛋白质组学分析表明，SFN影响细胞骨架的形成。后续实验证实，SFN显著抑制TGF-β1诱导的肌动蛋白应激纤维形成以及与肌动蛋白应激纤维形成相关的蛋白质的表达，包括桩蛋白、IQGAP1、黏着斑激酶、PAK2和ROCK。此外，SFN直接与RAF家族蛋白（包括ARAF、BRAF和CRAF）结合，并抑制MEK和ERK磷酸化。这些体外实验结果表明，SFN靶向RAF/MEK/ERK信号通路以抑制肌动蛋白应激纤维的形成，从而抑制乳腺癌细胞转移。
