Migration Of Human Bladder Cancer Cells Research Articles

Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway.

Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2), MMP-9, urokinase-type plasminogen activator receptor (uPAR), focal adhesion kinase (FAK), phosphatidylinositide-3 kinases (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, Ras homolog gene family, member A (Rho A), Ras, mitogen-activated protein kinase kinase 7 (MKK7) and mitogen-activated protein kinase kinase kinase 3 (MEKK3), and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in RT4 and T24 cells. This study revealed that flaccidoxide-13-acetate suppressed cell migration and invasion by reducing the expressions of MMP-2 and MMP-9, regulated by the FAK/PI3K/AKT/mTOR pathway. In conclusion, our study was the first to demonstrate that flaccidoxide-13-acetate could be a potent medical agent for use in controlling the migration and invasion of bladder cancer.

Abstract 526: NFκB p65 overexpression promotes bladder cancer migration via FBW7-mediated degradation of RhoGDIα protein

Abstract Since bladder cancer (BC) is one of the most lethal urological malignant tumors worldwide, understanding the molecular mechanisms that trigger the migration, invasion and metastasis of BC has great significance in reducing the mortality of this disease. RelA/p65, a member of the NF-kappa B transcription factor family, is increasingly recognized as a crucial player in many steps of cancer initiation and progression. In this study, we unexpectedly found that p65 protein expression increased in the bladder carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced high invasive bladder tumor tissues, and in human bladder cancer cell lines. We also observed that p65 overexpression promoted bladder cancer cell migration by inhibiting RhoGDIα expression. We further demonstrate that the regulatory effect of p65 on RhoGDIα expression is mediated by its upregulation of FBW7, which specifically interacted with RhoGDIα and promoted RhoGDIα ubiquitination and degradation. Mechanistic studies revealed that p65 stabilizing the E3 ligase FBW7 protein was mediated by its attenuating Pten transcription. Taken together, p65 overexpression results in Pten downregulation, and FBW7 protein degradation, and in turn leading to RhoGDIα protein degration and promotings human BC cell migration. The identification of p65/PTEN/FBW7/RhoGDIα axis provides a significant insight into understanding the nature of BC migration. Note: This abstract was not presented at the meeting. Citation Format: Yang Li, Junlan Zhu, Jingxia Li, Chuanshu Huang. NFκB p65 overexpression promotes bladder cancer migration via FBW7-mediated degradation of RhoGDIα protein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 526. doi:10.1158/1538-7445.AM2017-526

MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion.

The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3'-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.