Department of Oncology, Fourth People's Hospital of Zibo, Zibo, Shandong, China.
Eur Rev Med Pharmacol Sci. 2018 May;22(10):3067-3073. doi: 10.26355/eurrev_201805_15066.
LIM homeobox domain 6 (LHX6) is emerging as a critical regulator in carcinogenesis and tumor progression. The previous study has reported the expression and function of LHX6 in breast cancer (BC). However, its mechanism underlying BC metastasis remains largely unclear. This study aimed to investigate the related mechanisms of the tumor-suppressive role of LHX6 in BC.
Quantitative Real-time PCR (qRT-PCR) and Western blotting were used to determine LHX6 mRNA levels and protein expressions in BC tissues and cell lines. LHX6 protein expression was also analyzed in BC tissues and matched normal breast tissues using immunohistochemistry (IHC). The biologic functions of LHX6 in BC were explored by CCK-8 assay, colony formation assay, and transwell assays in vitro. Finally, we investigated the effect of LHX6 up-regulation on PI3K/AKT/mTOR pathway by Western blot.
Our results showed that LHX6 was lowly expressed at the mRNA and protein level in BC cancer tissues and cell lines. Ectopic expression of LHX6 in MDA-MB-231 and T-47D suppressed cell growth, migration, and invasion. Mechanistically, our further investigations revealed that the upregulation of LHX6 inhibited the activation of the PI3K/Akt/mTOR signaling pathway.
We firstly provided evidence that LHX6 exerted its anti-tumor function on BC via suppressing activation of the PI3K/Akt/mTOR signaling, which eventually inhibited the progression of BC.
LIM 同源盒结构域 6(LHX6)在肿瘤发生和肿瘤进展中作为关键调节因子而出现。先前的研究已经报道了 LHX6 在乳腺癌(BC)中的表达和功能。然而,其在 BC 转移中的机制在很大程度上仍不清楚。本研究旨在探讨 LHX6 在 BC 中抑制肿瘤作用的相关机制。
使用定量实时 PCR(qRT-PCR)和 Western blot 法测定 BC 组织和细胞系中 LHX6 mRNA 水平和蛋白表达。免疫组织化学(IHC)分析 BC 组织和匹配的正常乳腺组织中的 LHX6 蛋白表达。体外 CCK-8 测定、集落形成测定和 Transwell 测定探讨 LHX6 在 BC 中的生物学功能。最后,我们通过 Western blot 研究了 LHX6 上调对 PI3K/AKT/mTOR 通路的影响。
我们的结果表明,LHX6 在 BC 癌组织和细胞系中的 mRNA 和蛋白水平均低表达。在 MDA-MB-231 和 T-47D 中过表达 LHX6 抑制细胞生长、迁移和侵袭。机制研究进一步表明,LHX6 的上调抑制了 PI3K/Akt/mTOR 信号通路的激活。
我们首次提供了证据表明,LHX6 通过抑制 PI3K/Akt/mTOR 信号通路的激活来发挥其对 BC 的抗肿瘤作用,从而最终抑制了 BC 的进展。