Department of Reproductive Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Section of Cancer Stem Cell Research, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of the People's Republic of China, Xi'an 710061, China.
Int J Mol Sci. 2023 Jan 5;24(2):1062. doi: 10.3390/ijms24021062.
SNAI2 (Snai2) is a zinc-finger transcriptional repressor that belongs to the Snail family. The accumulated evidence suggests that SNAI2 exhibits biphasic effects on regulating a stem-like phenotype in various types of cells, both normal and malignant. In this study, by exogenously expressing SNAI2 in SiHa cells, SNAI2 exhibited the capacity to inhibit a stem-like phenotype in cervical cancer cells. The SNAI2-overexpressing cells inhibited cell growth, tumorsphere formation, tumor growth, enhanced sensitivity to cisplatin, reduced stem cell-related factors' expression, and lowered tumor initiating frequency. In addition, the EPCAM cells sorted from SiHa cells exhibited an enhanced capacity to maintain a stem-like phenotype. Further study demonstrated that the trans-suppression of EPCAM expression by SNAI2 led to blockage of the nuclear translocation of β-catenin, as well as reduction in SOX2 and c-Myc expression in SiHa and HeLa cells, but induction in SNAI2 knockdown cells (CaSki), which would be responsible for the attenuation of the stem-like phenotype in cervical cancer cells mediated by SNAI2. All of these results demonstrated that SNAI2 could attenuate the stem-like phenotype in cervical cancer cells through the EPCAM/β-catenin axis.
SNAI2(Snai2)是一种锌指转录阻遏物,属于Snail 家族。越来越多的证据表明,SNAI2 在调节各种类型细胞的干性表型方面表现出双相作用,包括正常细胞和恶性细胞。在本研究中,通过在 SiHa 细胞中外源性表达 SNAI2,SNAI2 表现出抑制宫颈癌干细胞样表型的能力。过表达 SNAI2 的细胞抑制细胞生长、肿瘤球形成、肿瘤生长、增加顺铂敏感性、降低干细胞相关因子的表达,并降低肿瘤起始频率。此外,从 SiHa 细胞中分选的 EPCAM 细胞表现出增强维持干细胞样表型的能力。进一步的研究表明,SNAI2 对 EPCAM 表达的转录抑制导致β-catenin 的核易位受阻,并降低 SiHa 和 HeLa 细胞中 SOX2 和 c-Myc 的表达,但在 SNAI2 敲低细胞(CaSki)中诱导,这将负责衰减由 SNAI2 介导的宫颈癌干细胞样表型。所有这些结果表明,SNAI2 可以通过 EPCAM/β-catenin 轴来减弱宫颈癌干细胞样表型。