Department of Applied Biology and Food Sciences, Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-cho, Hirosaki, Aomori 036-8561, Japan.
Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Int J Mol Sci. 2019 Sep 22;20(19):4697. doi: 10.3390/ijms20194697.
Cervical cancer with early metastasis of the primary tumor is associated with poor prognosis and poor therapeutic outcomes. Since epithelial-to-mesenchymal transition (EMT) plays a role in acquisition of the ability to invade the pelvic lymph nodes and surrounding tissue, it is important to clarify the molecular mechanism underlying EMT in cervical cancer. RhoE, also known as Rnd3, is a member of the Rnd subfamily of Rho GTPases. While previous reports have suggested that RhoE may act as either a positive or a negative regulator of cancer metastasis and EMT, the role of RhoE during EMT in cervical cancer cells remains unclear. The present study revealed that RhoE expression was upregulated during transforming growth factor-β (TGF-β)-mediated EMT in human cervical cancer HeLa cells. Furthermore, reduced RhoE expression enhanced TGF-β-mediated EMT and migration of HeLa cells. In addition, we demonstrated that RhoE knockdown elevated RhoA activity and a ROCK inhibitor partially suppressed the acceleration of TGF-β-mediated EMT by RhoE knockdown. These results indicate that RhoE suppresses TGF-β-mediated EMT, partially via RhoA/ROCK signaling in cervical cancer HeLa cells.
宫颈癌伴原发性肿瘤早期转移与预后不良和治疗效果差有关。由于上皮间质转化（EMT）在获得侵袭盆腔淋巴结和周围组织的能力中起作用，因此阐明宫颈癌中 EMT 的分子机制很重要。RhoE，也称为 Rnd3，是 Rho GTPase 的 Rnd 亚家族的成员。虽然之前的报告表明 RhoE 可能作为癌症转移和 EMT 的正调节剂或负调节剂发挥作用，但 RhoE 在宫颈癌细胞 EMT 过程中的作用尚不清楚。本研究表明，RhoE 在人宫颈癌 HeLa 细胞 TGF-β 介导的 EMT 过程中表达上调。此外，降低 RhoE 表达增强了 TGF-β 介导的 EMT 和 HeLa 细胞迁移。此外，我们证明 RhoE 敲低可提高 RhoA 活性，ROCK 抑制剂部分抑制了 RhoE 敲低对 TGF-β 介导的 EMT 的加速作用。这些结果表明，RhoE 通过 RhoA/ROCK 信号通路抑制宫颈癌 HeLa 细胞中的 TGF-β 介导的 EMT。
