CAB39 mediates epithelial-mesenchymal transition via the activation of NF-kB signaling, facilitating bladder cancer invasion and metastasis
CAB39 mediates epithelial-mesenchymal transition via the activation of NF-kB signaling, facilitating bladder cancer invasion and metastasis
复制标题
CAB39通过激活NF-kB信号介导上皮间质转化，促进膀胱癌侵袭和转移
作者：
Lifen Peng;Haichao Chao;Leihong Deng;Zhaojun Yu;Huanhuan Deng;Fanghua Xu;Xiangda Xu;Jianbiao Huang;Tao Zeng
膀胱癌（BC）是男性最常见的泌尿系统癌症。本研究旨在明确钙结合蛋白39 （CAB39）在正常和肿瘤组织中的表达模式，并探讨其在人乳腺癌上皮间充质转化（EMT）中的生物学功能。为此，采用免疫组织化学和定量反转录(RT)-PCR分析方法检测CAB39在BC组织和细胞系中的表达。通过shRNA敲除CAB39的细胞系的伤口愈合实验、细胞侵袭实验和CCK8增殖实验，以及裸鼠异种移植肿瘤模型，评估CAB39减少对BC细胞侵袭、迁移和增殖的影响。利用基因集富集分析（Gene Set Enrichment Analysis， GSEA）数据库分析BC细胞中CAB39表达增加后富集的基因面板，并通过western blot分析验证。我们发现CAB39在BC组织和细胞中表达上调，其表达与恶性疾病的预后呈负相关。在T24和5637细胞系中，shrna介导的内源性CAB39的衰减逆转了这种侵袭和转移作用，这在裸鼠异种移植物的肿瘤发生抑制中得到了证明。此外，CAB39可能通过核因子κ B （NF-kB）信号通路，通过上调BC中N-cadherin和下调E-cadherin介导EMT，这为未来研究CAB39作为开发新型治疗BC药物的潜在靶点提供了理论依据。
Bladder cancer (BC) is the most common urinary cancer among men. The aim of this research was to define the expression patterns of calcium binding protein 39 (CAB39)in normal and tumor tissues and explore its biological function in epithelial mesenchymal transition (EMT) in human BC. For this purpose, immunohistochemistry and Quantitative reverse transcription (RT)-PCR analyses were used to examine the expression of CAB39 in BC tissues and cell lines. Wound-healing assay, cell invasion assay, and CCK8 proliferation assay in cell lines in which CAB39 was knocked down by shRNA, as well as xenograft tumor models in nude mice, were performed to assess the effect of CAB39 reduction on the invasion, migration, and proliferation of BC cells. The Gene Set Enrichment Analysis (GSEA) database was used to analyze panel of genes enriched after increased CAB39 expression in BC cells, which were validated by western blot analysis. It was found that CAB39 was upregulated in BC tissues and cells, while its expression was inversely correlated with the prognosis of the malignant disease. The shRNA-mediated attenuation of endogenous CAB39 in the T24 and 5637 cell lines reversed such invasive and metastatic effects, as demonstrated by the inhibition of tumorigenesis in nude mice xenografts. Furthermore, CAB39 could mediate EMT through the upregulation of N-cadherin and downregulation of E-cadherin in BC via the nuclear factor kappa B (NF-kB) signaling pathway, which provides a rationale for future investigation of CAB39 as a potential target for the development of novel therapeutic agents to fight BC.