Department of Otorhinolaryngology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
Department of Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen, China.
PLoS One. 2019 Apr 11;14(4):e0215299. doi: 10.1371/journal.pone.0215299. eCollection 2019.
Steroid receptor coactivator 1 (Src-1) and Twist1 are aberrantly upregulated in a variety of tumors and play an important role in tumor progression. However, the exact role of Src-1 and Twist1 in nasopharyngeal carcinoma (NPC) is uncertain. In this study, we investigated the possible prognostic value and biological effect of Src-1 and Twist1 in NPC. Src-1 and Twist1 expression was detected in a cohort of NPC patients (n = 134) by qRT-PCR. Kaplan-Meier survival analysis was used comparing overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional hazard regression model. Biologic effect of Src-1 and Twist1 in NPC cell lines was evaluated by western blot, colony formation assay, soft agar assay, scratch wound healing assay, transwell invasion assay and tumor xenografts growth. We have found that Src-1 and Twist1 were aberrantly upregulated in human NPC tissues, and associated with advanced tumor stage, distant metastasis and unfavorable prognosis. Knockdown of Src-1 or Twist1 in human NPC cell line CNE-1 suppressed colony formation, anchorage-independent growth, cell migration, invasion and tumor xenografts growth, while enforced expression of Src-1 or Twist1 in human NPC cell line HNE-2 promotes anchorage-independent growth, cell migration and invasion. In addition, Src-1 and Twist1 could suppress E-cadherin expression and increase Vimentin expression, thus suggested that Src-1 and Twist1 enhanced the malignant behaviors of NPC cells via inducing epithelial-mesenchymal transition (EMT). Our data indicated that Src-1 and Twist1 could be possible prognostic biomarkers and potential therapy targets for patients with NPC.
类固醇受体共激活因子 1（Src-1）和 Twist1 在多种肿瘤中异常上调，在肿瘤进展中发挥重要作用。然而，Src-1 和 Twist1 在鼻咽癌（NPC）中的确切作用尚不确定。在这项研究中，我们研究了 Src-1 和 Twist1 在 NPC 中的可能预后价值和生物学效应。通过 qRT-PCR 检测了一组 NPC 患者（n=134）中 Src-1 和 Twist1 的表达。使用 Kaplan-Meier 生存分析比较总生存期（OS）和无进展生存期（PFS）。使用 Cox 比例风险回归模型进行多变量分析。通过 Western blot、集落形成实验、软琼脂实验、划痕愈合实验、Transwell 侵袭实验和肿瘤异种移植生长实验评估 Src-1 和 Twist1 在 NPC 细胞系中的生物学效应。我们发现 Src-1 和 Twist1 在人 NPC 组织中异常上调，并与晚期肿瘤分期、远处转移和不良预后相关。在人 NPC 细胞系 CNE-1 中敲低 Src-1 或 Twist1 抑制集落形成、锚定非依赖性生长、细胞迁移、侵袭和肿瘤异种移植生长，而在人 NPC 细胞系 HNE-2 中强制表达 Src-1 或 Twist1 促进锚定非依赖性生长、细胞迁移和侵袭。此外，Src-1 和 Twist1 可以抑制 E-钙粘蛋白的表达并增加波形蛋白的表达，从而提示 Src-1 和 Twist1 通过诱导上皮-间充质转化（EMT）增强 NPC 细胞的恶性行为。我们的数据表明，Src-1 和 Twist1 可能是 NPC 患者的可能预后生物标志物和潜在治疗靶点。
