Sonic Hedgehog stimulates migration of MCF-7 breast cancer cells through Rac1

T. Shen, Bo’ang Han, Y. Leng, Sen Yan, Junfeng Shi, S. Yue, Steven Y. Cheng
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引用次数: 1

Abstract

As one of the most common tumors in women, breast cancer has drawn considerable interest from investigators and clinicians in recent years. Despite early diagnosis and best therapeutic regimens available, the prognosis of malignant or metastatic breast cancer patients is still not optimistic. Hedgehog signaling, a classical pathway indispensable to embryonic development, participates in the growth of a variety of tumors. In the present study, the effect of Sonic Hedgehog (Shh) on breast cancer cells was investigated. We identified that Shh signal stimulated the migration of MCF-7 breast cancer cells. Smo and Gli1 were involved in Shh-stimulated migration of MCF-7 cells. Activating Smo and Gli1 induced cell migration, which was blocked by their specific antagonists. The effect of Shh signaling on MCF-7 cells was independent of Wnt5a, Dvl2 and Rab35, but directly dependent on Rac1. In conclusion, our study suggested that Shh promotes breast cancer cell migration via Rac1 independently of the non-canonical Wnt signaling pathway, which may represent a rational molecular target for combination medication in breast cancer.
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Sonic Hedgehog通过Rac1刺激MCF-7乳腺癌细胞的迁移
作为女性最常见的肿瘤之一,乳腺癌近年来引起了研究者和临床医生的极大兴趣。尽管早期诊断和最好的治疗方案,恶性或转移性乳腺癌患者的预后仍然不容乐观。Hedgehog信号是胚胎发育不可或缺的经典信号通路,参与多种肿瘤的生长。本研究探讨了Sonic Hedgehog基因(Shh)对乳腺癌细胞的影响。我们发现Shh信号刺激MCF-7乳腺癌细胞的迁移。Smo和Gli1参与了sh刺激的MCF-7细胞迁移。激活Smo和Gli1可诱导细胞迁移,而这一过程被它们的特异性拮抗剂阻断。Shh信号对MCF-7细胞的作用不依赖于Wnt5a、Dvl2和Rab35,而直接依赖于Rac1。综上所述,我们的研究表明Shh独立于非规范的Wnt信号通路,通过Rac1促进乳腺癌细胞迁移,这可能是乳腺癌联合用药的合理分子靶点。
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