王芫, 郭忠英, 周倩, 李进, 何敬东. Cdc42EP3对结直肠癌细胞迁移和侵袭的影响[J]. 中国肿瘤临床, 2023, 50(11): 541-549. DOI: 10.12354/j.issn.1000-8179.2023.20221600
引用本文: 王芫, 郭忠英, 周倩, 李进, 何敬东. Cdc42EP3对结直肠癌细胞迁移和侵袭的影响[J]. 中国肿瘤临床, 2023, 50(11): 541-549. DOI: 10.12354/j.issn.1000-8179.2023.20221600
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Yuan Wang, Zhongying Guo, Qian Zhou, Jin Li, Jingdong He. Effects of Cdc42EP3 on migration and invasion of colorectal cancer cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(11): 541-549. DOI: 10.12354/j.issn.1000-8179.2023.20221600
Citation: Yuan Wang, Zhongying Guo, Qian Zhou, Jin Li, Jingdong He. Effects of Cdc42EP3 on migration and invasion of colorectal cancer cells[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(11): 541-549. DOI: 10.12354/j.issn.1000-8179.2023.20221600
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Cdc42EP3对结直肠癌细胞迁移和侵袭的影响

Effects of Cdc42EP3 on migration and invasion of colorectal cancer cells

    摘要
  • 摘要:
      目的  探讨Cdc42EP3在结直肠癌（colorectal cancer，CRC）转移中的作用及相关作用机制。
      方法  回顾性收集2010年12月至2011年12月于南京医科大学附属淮安第一医院诊治的97例CRC患者的术后病理蜡块，同时收集相关临床病理资料。采用免疫组织化学法检测Cdc42EP3在癌组织与相应正常组织中的表达，随后通过统计学方法分析差异表达，并评估表达水平与临床病理学参数及生存预后之间的相关性。干扰CRC细胞Cdc42EP3的表达后，应用Transwell技术检测Cdc42EP3对CRC细胞的迁移及侵袭能力的影响，并使用Western blot技术检测EMT相关蛋白的表达。通过基因芯片技术及生物信息学分析预测Cdc42EP3的下游靶点STAT1，并通过回复实验验证。
      结果  Cdc42EP3在癌组织中的表达水平显著高于相应正常组织（P<0.001），并与肿瘤的淋巴结转移（P=0.011）、TNM分期（P=0.008）及患者生存预后（P<0.001）之间呈显著相关性。干扰Cdc42EP3表达后，CRC细胞的迁移及侵袭能力均明显减弱（P<0.01）。预测出Cdc42EP3的下游靶点STAT1。在CRC细胞中，干扰Cdc42EP3表达可提高内源性STAT1蛋白水平，过表达STAT1具有与Cdc42EP3表达下降类似的肿瘤抑制作用，而STAT1表达下降可削弱Cdc42EP3敲低所致的肿瘤抑制作用（P<0.05）。
      结论   Cdc42EP3在CRC组织中高表达。Cdc42EP3通过调控STAT1的表达促进CRC细胞的迁移及侵袭。

     

    Abstract:
      Objective  To investigate the role of Cdc42EP3 in colorectal cancer (CRC) metastasis and its related mechanism.
      Methods  The pathological wax blocks of 97 CRC patients diagnosed and treated at The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from December 2010 to December 2011 were collected retrospectively, and the relevant clinicopathologic data were collected simultaneously. An immunohistochemistry assay was used to assess the expression of the Cdc42EP3 protein in cancer and corresponding normal tissues. Thereafter, statistical methods were used to analyze the differential expression and evaluate correlations between the expression levels, clinicopathologic parameters, and survival outcomes. A loss-of-function assay was performed on CRC cell lines with high Cdc42EP3 messenger RNA expression levels, and changes in cell migration and invasion abilities were detected via Transwell assays. EMT-associated protein levels were further tested using the Western blot assays. Gene chip technology, bioinformatics analysis, and rescue experiments showed that Cdc42EP3 promoted the migration and invasion of CRC cells through STAT1.
      Results  Cdc42EP3 was highly expressed in CRC tissues compared with the adjacent normal epithelial tissues (P<0.001), and its expression was associated with lymph node metastasis (P=0.011), TNM stage (P=0.008), and a poor patient prognosis (P<0.001). Correspondingly, Cdc42EP3 promoted migration and invasion in vitro (P<0.01). Bioinformatic data suggested that Cdc42EP3 targeted STAT1. Suppression of Cdc42EP3 expression in CRC cell lines increased endogenous STAT1 protein levels. STAT1 overexpression mimicked the tumor suppressive effect of Cdc42EP3 knockdown on CRC cells, while STAT1 knockdown abolished the tumor suppressive effect of Cdc42EP3 knockdown on CRC cells (P<0.05).
      Conclusions  When combined, our results suggest that Cdc42EP3 expresses highlyin CRC tissues and plays a metastasis-promoting role via STAT1 in CRC cells and, thus, could be a target for preventing metastasis.

     

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