|
- 2016
Sox2通过Wnt信号通路对宫颈癌侵袭及迁移能力的影响
|
Abstract:
摘要:目的 探讨干细胞转录因子Sox2对宫颈鳞癌SiHa细胞侵袭及迁移能力的影响及其机制。方法 采用RT-PCR及Western blot方法分别检测本实验前期构建的稳定高表达Sox2的SiHa-Sox2细胞及对照组SiHa-EGFP细胞中Sox2的表达情况;细胞划痕实验及Transwell小室实验观察Sox2对SiHa细胞侵袭及迁移能力的影响;Western blot检测两组细胞中Wnt信号通路关键基因β-catenin的表达情况。结果 稳定表达Sox2的SiHa-Sox2细胞中Sox2的mRNA及蛋白表达均明显增加;SiHa-Sox2组细胞侵袭及迁移能力增强;Western blot检测结果显示β-catenin表达上调。结论 Sox2通过上调β-catenin的表达激活Wnt信号通路,使宫颈鳞癌SiHa细胞的侵袭及迁移能力增强,从而促进宫颈鳞癌的发生发展。
ABSTARCT: Objective To investigate the effects of the transcription factor SRY-related high-mobility-group box 2 (Sox2) related to stem cells on the invasion and migration of cervical squamous carcinoma cell line SiHa and its mechanism. Methods The expression of Sox2 was detected in Sox2 stably over-expressed cell line SiHa-Sox2 and negative control SiHa-EGFP cells by RT-PCR and Western blotting, respectively. The effects of Sox2 on the invasion and migration capacities of SiHa cells were detected by wound-healing assay and transwell assay. The expression of β-catenin was detected by Western blot. Results Compared with that of SiHa-EGFP cells, the expression of Sox2 at both mRNA and protein levels was obviously upregulated in SiHa-Sox2 cells. The migration and invasion capacities of SiHa-Sox2 cells were increased significantly (P<0.01), and the expression of β-catenin increased dramatically compared with that of the control cells. Conclusion Sox2 promotes the invasion and migration capacities of SiHa cells by increasing the expression of β-catenin and activating Wnt signaling pathway, which contributes to the development of cervical cancer
[1] | BASU-ROY U, SEO E, RAMANATHAPURAM L, et al. Sox2 maintains self-renewal of tumor-initiating cells in osteosarcomas[J]. Oncogene, 2012, 31(18):2270-2282. |
[2] | NEUMANN J, BAHR F, HORST D, et al. SOX2 expression correlates with lymph-node metastases and distant spread in right-side colon cancer[J]. BMC Cancer, 2011, 11:518. |
[3] | 冀静,宁芬茹,刘海娟. Sox2对宫颈鳞癌细胞增殖能力影响的研究[J].四川大学学报(医学版),2014, 45(5):785-788. |
[4] | LI X, XU Y, CHEN Y, et al. Sox2 promtes tumor metasis by stimulating epithelial-to-mesenchymal transition via regulation of WNT/β-catenin signal network[J]. Cancer Lett, 2013, 336(2):379-389. |
[5] | YE X, WU F, WU C, et al. β-Catenin, a Sox2 binding partner, regulates the DNA binding and transcriptional activity of Sox2 in breast cancer cells[J]. Cell Signal, 2013, 26(3):492-501. |
[6] | CHEN Y, HUANG Y, HUANG Y, et al. The prognostic value of SOX2 expression in non-small cell lung cancer: A meta-analysis[J]. PLoS One, 2013, 8(8):e71140. |
[7] | VAZQUEZ-MARTIN A, CUF?P S, L?PEZ-BONET E, et al. Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2 enhances the tumor-initiating capacity of breast cancer cells[J]. Cell Cycle, 2013, 12(22)3471-3477. |
[8] | KORMISH JD, SINNER D, ZORN AM, et al. Interactions between SOX factors and Wnt/β-catenin signaling in development and disease[J]. Dev Dyn, 2010, 239(1):56-58. |
[9] | 魏星,冀静,宁芬茹. Sox-2及WNT信号通路在宫颈癌中的表达及相互作用[J]. 西安交通大学学报(医学版),2013, 34(6):813-817. |
[10] | SUN C, SUN L, LI Y, et al. Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug[J]. Med Oncol, 2013, 30(2):1-10. |
[11] | XU F, WANG H, ZHANG X, et al. Cell proliferation and invasion ability of human choriocarcinoma cells lessened due to inhibition of Sox2 expression by microRNA-145[J]. Exp Ther Med, 2013, 5(1):77-84. |
[12] | GEN Y, YASUI K, NISHIKAWA T, et al. SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway[J]. Cancer Science, 2013, 104(7):810-816. |
[13] | LOU X, HAN X, JIN C,et al. SOX2 targets fibronectin 1 to promote cell migration and invasion in ovarian cancer: new molecular leads for therapeutic intervention[J]. OMICS, 2013, 17(10):510-518. |