Delta Np63 promotes UMJJC-3 cell invasiveness and migration through claudin-1 in vitro

作者:Jing Peng; Zou Jiaqiong; Zhang Jun; Jiang Xingliang*
来源:Molecular Medicine Reports, 2013, 7(3): 1026-1030.
DOI:10.3892/mmr.2013.1271

摘要

The p63 gene, a member of the p53 gene family, has two different promoter usage-generating proteins that contain or lack (Delta N) an NH2-terminus. Although p53 and p63 have high sequence and structural similarities, the molecules differ in function and expression profiles. p63 is critical for the development of epithelial organs or tissues, including the epidermis and other squamous epithelia, as well as the salivary, lachrymal, mammary and prostate glands and the urothelium. In addition, p63 is essential for the proliferative potential of stem cells in the epidermis. In contrast to p53, the role of Delta Np63 in tumors remains unclear and complex. Our previous study demonstrated that Delta Np63 is overexpressed in human bladder carcinoma tissues. The mechanism by which Delta Np63 promotes tumor cell development, including adhesion, proliferation and polarity, is unknown. Data demonstrate that Delta Np63 induces the invasiveness of cancer cells through specific downstream genes and the mechanism is associated with cell junctions. Claudin-1 is an important p63 target gene for normal skin development. Claudin-1, as a connexin, functions in a similar manner to other connexins to affect important events during cancer cell development. In the present study, Delta Np63 gene expression in bladder tumor tissues was found to be significantly higher than that in normal tissue, indicating that Delta Np63 is localized to the nucleus. In addition, Delta Np63 silencing decreased invasion and metastasis in UM-UC-3 cells and reduced claudin-1 expression.

  • 出版日期2013-3

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