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LIM 蛋白 JUB 促进结直肠癌中的上皮-间质转化。

LIM protein JUB promotes epithelial-mesenchymal transition in colorectal cancer.

机构信息

Department of Gastroenterology, Zengcheng People's Hospital (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, China.

出版信息

Cancer Sci. 2014 Jun;105(6):660-6. doi: 10.1111/cas.12404. Epub 2014 May 10.

Abstract

Metastasis is the leading cause of cancer-related death in almost all types of cancers, including colorectal cancer (CRC). Metastasis is a complex, multistep, dynamic biological event, and epithelial-mesenchymal transition (EMT) is a critical process during the cascade. Ajuba family proteins are LIM domain-containing proteins and are reported to be transcription repressors regulating different kinds of physiological processes. However, the expression and pathological roles of Ajuba family proteins in tumors, especial in tumor metastasis, remain poorly studied. Here, we found that JUB, but not the other Ajuba family proteins, was highly upregulated in clinical specimens and CRC cell lines. Ectopic expression of JUB induced EMT and enhanced motility and invasiveness in CRC, and vice versa. Mechanistic study revealed that JUB induces EMT via Snail and JUB is also required for Snail-induced EMT. The expression of JUB shows an inverse correlation with E-cadherin expression in clinical specimens. Taken together, these findings revealed that the LIM protein JUB serves as a tumor-promoting gene in CRC by promoting EMT, a critical process of metastasis. Thus, the LIM protein JUB may provide a novel target for therapy of metastatic CRC.

摘要

转移是几乎所有类型癌症(包括结直肠癌)相关死亡的主要原因。转移是一个复杂的、多步骤的、动态的生物学事件,上皮-间充质转化(EMT)是级联反应中的一个关键过程。Ajuba 家族蛋白是 LIM 结构域蛋白,据报道是调节各种生理过程的转录抑制剂。然而,Ajuba 家族蛋白在肿瘤中的表达和病理作用,特别是在肿瘤转移中,仍然研究甚少。在这里,我们发现 JUB(而非其他 Ajuba 家族蛋白)在临床标本和 CRC 细胞系中高度上调。JUB 的异位表达诱导 EMT,并增强 CRC 的运动性和侵袭性,反之亦然。机制研究表明 JUB 通过 Snail 诱导 EMT,并且 JUB 也是 Snail 诱导的 EMT 所必需的。JUB 的表达与临床标本中 E-钙粘蛋白的表达呈负相关。总之,这些发现表明 LIM 蛋白 JUB 通过促进 EMT(转移的关键过程)在 CRC 中充当促进肿瘤的基因。因此,LIM 蛋白 JUB 可能为转移性 CRC 的治疗提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23b7/4317901/fec55785907d/cas0105-0660-f1.jpg

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