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

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.

• Authors: Xing-Hua Liang, Guang-Xian Zhang, Yue-Bin Zeng, Hai-Feng Yang, Wen-Hong Li, Qi-Long Liu, Yue-Liang Tang, Wen-Guang He, Yan-Nian Huang, Lei Zhang, Li-Na Yu, Xian-Cheng Zeng
• Journal: Cancer science (Cancer Sci) Vol. 105 Issue 6 Pg. 660-6 (Jun 2014) ISSN: 1349-7006 [Electronic] England
• PMID: 24673742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Chemical References

• AJUBA protein, human
• Cadherins
• LIM Domain Proteins
• RNA, Small Interfering
• Snail Family Transcription Factors
• Transcription Factors

Topics

• Caco-2 Cells
• Cadherins (biosynthesis)
• Cell Movement
• Colorectal Neoplasms (genetics, pathology)
• Epithelial-Mesenchymal Transition
• HCT116 Cells
• Humans
• LIM Domain Proteins (genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• RNA Interference
• RNA, Small Interfering
• Signal Transduction
• Snail Family Transcription Factors
• Spheroids, Cellular (pathology)
• Transcription Factors (metabolism)
• Tumor Cells, Cultured
• Up-Regulation