ARHGAP4 regulates the cell migration and invasion of pancreatic cancer by the HDAC2/β-catenin signaling pathway. (8th April 2019)

• Record Type: Journal Article
• Authors: Shen, Yehua; Xu, Litao; Ning, Zhouyu; Liu, Luming; Lin, Junhua; Chen, Hao; Meng, Zhiqiang
• Is Part Of: Carcinogenesis. Volume 40:Number 11(2019)
• Page Start: 1405
• Page End: 1414
• Publication Date: 2019-04-08
• Subjects: Carcinogenesis -- Periodicals; Cancer -- Genetic aspects -- Periodicals; Cancer -- Prevention -- Periodicals; Cancer -- Periodicals; 616.994071
• DOI: 10.1093/carcin/bgz067
• Languages: English
• ISSNs: 0143-3334

Abstract

Abstract: β-catenin is a subunit of the cadherin protein complex and acts as an intracellular signal transducer in the Wnt signaling pathway that mediates multiple cellular processes, such as cell migration and invasion. HDAC2 (histone deacetylase 2), a deacetylase that maintains histone H3 in a deacetylated state in the promoter region of Wnt-targeted genes where β-catenin is bound, negatively regulating β-catenin activation. However, the regulation of HDAC2/β-catenin pathway remains unclear. Here, we report ARHGAP4 as a new regulator of the β-catenin pathway that regulates cell invasion and migration of pancreatic cancer as well as the downstream effector MMP2 and MMP9 expression in vitro . Mechanistically, ARHGAP4 interacts with and ubiquitinates HDAC2, which in turn inhibits β-catenin activation. Furthermore, treatment of CAY10683, an HDAC2 inhibitor, and XAV939, a Wnt/β-catenin pathway inhibitor, attenuated the effects of ARHGAP4 silencing on pancreatic cancer cells. Overall, our findings establish ARHGAP4 as a novel regulator of HDAC2/β-catenin pathway with a critical role in tumorigenesis. Abstract : ARHGAP4 as a new regulator of the β-catenin pathway regulates cell invasion and migration of pancreatic cancer as well as the downstream effectors MMP2 and MMP9 expression. Mechanistically, ARHGAP4 ubiquitinates HDAC2, contributing to inhibit β-catenin activation.