TITLE

CXCL1/GROα increases cell migration and invasion of prostate cancer by decreasing fibulin-1 expression through NF-κB/HDAC1 epigenetic regulation

AUTHOR(S)
Kuo, Po-Lin; Shen, Kun-Hung; Hung, Shun-Hsing; Hsu, Ya-Ling
PUB. DATE
December 2012
SOURCE
Carcinogenesis;Dec2012, Vol. 33 Issue 12, p2477
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castration-resistant prostate cancer (CRPC), has not been investigated. We explored whether CXCL1/GROα enhances cell migration and invasion in PC-3 and DU145 CRPC. Induction of PC-3 and DU145 cancer progression by CXCL1/GROα is associated with increased AKT activation and IκB kinase α (IKKα) phosphorylation, resulting in nuclear factor-kappaB (NF-κB) activation. Activated NF-κB interacts with histone deacetylase 1 (HDAC1) to form a gene-silencing complex, which represses the expression of fibulin-1D by decreasing the acetylation of histone H3 and H4 on the NF-κB-binding site of the fibulin-1D promoter. Blockade of AKT2 by small hairpin RNA (shRNA) decreases IKKα phosphorylation, NF-κB nuclear translocation and cell migration, indicating that AKT is required in CXCL1/GROα-mediated NF-κB activation and cell migration. In addition, NF-κB and HDAC1 shRNA decrease the effect of CXCL1/GROα on fibulin-1D downregulation, migration and invasion, suggesting that the NF-κB/HDAC1 complex is also involved in CXCL1/GROα-mediated cancer progression. Our findings provide the first evidence that CXCL1/GROα decreases fibulin-1D expression in prostate cancer cells and also reveals novel insights into the mechanism by which CXCL1/GROα regulates NF-κB activation through the AKT pathway. Our results also clearly establish that co-operation of NF-κB and HDAC1 regulates fibulin-1D expression by epigenetic modification. Our study suggests that inhibition of CXCL1/GROα-mediated AKT/NF-κB signaling may be an attractive therapeutic target for CRPC.
ACCESSION #
83942442

 

Related Articles

  • S100A8 and S100A9 Induce Cytokine Expression and Regulate the NLRP3 Inflammasome via ROS-Dependent Activation of NF-κB1. Simard, Jean-Christophe; Cesaro, Annabelle; Chapeton-Montes, Julie; Tardif, Mélanie; Antoine, Francis; Girard, Denis; Tessier, Philippe A. // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    S100A8 and S100A9 are cytoplasmic proteins expressed by phagocytes. High concentrations of these proteins have been correlated with various inflammatory conditions, including autoimmune diseases such as rheumatoid arthritis and Crohn’s disease, as well as autoinflammatory diseases. In the...

  • 14-3-3β Promotes Migration and Invasion of Human Hepatocellular Carcinoma Cells by Modulating Expression of MMP2 and MMP9 through PI3K/Akt/NF-κB Pathway. Tang, Yufu; Lv, Pengfei; Sun, Zhongyi; Han, Lei; Zhou, Wenping // PLoS ONE;1/5/2016, Vol. 11 Issue 1, p1 

    14-3-3β has been demonstrated to possess the oncogenic potential, and its increased expression has been detected in multiple types of carcinomas. However, majority of previous studies focused on the role of 14-3-3β in tumor cell proliferation and apoptosis, leaving much to be elucidated...

  • miR-451 inhibits cell proliferation in human hepatocellular carcinoma through direct suppression of IKK-β. Li, He-Ping; Zeng, Xian-Cheng; Zhang, Bing; Long, Jian-Ting; Zhou, Bo; Tan, Guo-Sheng; Zeng, Wei-Xia; Chen, Wei; Yang, Jian-Yong // Carcinogenesis;Nov2013, Vol. 34 Issue 11, p2443 

    It has been demonstrated that nuclear factor-kappa B (NF-κB), which is overactivated in hepatocellular carcinoma (HCC), plays important roles in the development of HCC. Recently, a group of dysregulated micro RNAs were reported to be involved in HCC progression. Further understanding of micro...

  • Regulation of cytokine signaling pathways by PIAS proteins. Shuai, Ke // Cell Research;Feb2006, Vol. 16 Issue 2, p196 

    Cytokines activate multiple signal transduction pathways to regulate gene expression. STATs and NF-kB are two important families of transcription factors activated by cytokines. Abnormal regulation of STAT and NF-kB activities has been associated with human diseases. The protein inhibitor of...

  • Mechanical stretch enhances NF-κB-dependent gene expression and poly(ADP-ribose) synthesis in synovial cells. Morisugi, Toshiaki; Tanaka, Yasuharu; Kawakami, Tetsuji; Kirita, Tadaaki // Journal of Biochemistry;May2010, Vol. 147 Issue 5, p633 

    Temporomandibular joint disorders (TMD) show complex symptoms associated with inflammation, pain and degeneration of the peripheral tissues including synovium. Although it is believed that excessive mechanical stress on synovium causes development of TMD, the molecular mechanism by which...

  • Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase. Park, Hye-Jeong; Youn, Hyung-Sun // Toxicology & Industrial Health;Mar2013, Vol. 29 Issue 2, p169 

    Nuclear factor-κB (NF-κB) is a transcription factor that mediates the inducible expression of a variety of genes involved in immune and inflammatory responses. NF-κB activation induces numerous proinflammatory gene products including cytokines, cyclooxygenase-2 (COX-2), and inducible...

  • Suppression of Inflammatory Cytokine Secretion by an NF-κB Inhibitor DHMEQ in Nasal Polyps Fibroblasts. Valera, Fabiana C.P.; Umezawa, Kazuo; Brassesco, María S.; Castro-Gamero, Angel M.; Queiroz, Rosane G.P.; Scrideli, Carlos A.; Tone, Luiz G.; Anselmo-Lima, Wilma T. // Cellular Physiology & Biochemistry (Karger AG);2012, Vol. 29 Issue 5/6, p13 

    Background: NF-κB is an essential transcription factor strongly associated to inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP). DHMEQ is a NF-κB inhibitor that has been previously described with a greatpotential indecreasing inflammation in diseases other than...

  • TLR9 and NF-κB Are Partially Involved in Activation of Human Neutrophils by Helicobacter pylori and Its Purified DNA. Alvarez-Arellano, Lourdes; Cortés-Reynosa, Pedro; Sánchez-Zauco, Norma; Salazar, Eduardo; Torres, Javier; Maldonado-Bernal, Carmen // PLoS ONE;Jul2014, Vol. 9 Issue 7, p1 

    Helicobacter pylori infection represents one of the most common bacterial infections worldwide. The inflammatory response to this bacterium involves a large influx of neutrophils to the lamina propria of the gastric mucosa. However, little is known about the receptors and molecular mechanisms...

  • miR-365 Promotes Cutaneous Squamous Cell Carcinoma (CSCC) through Targeting Nuclear Factor I/B (NFIB). Zhou, Meijuan; Zhou, Liang; Zheng, Li; Guo, Ling; Wang, Yinghui; Liu, Hongxia; Ou, Chengshan; Ding, Zhenhua // PLoS ONE;Jun2014, Vol. 9 Issue 6, p1 

    Aberrant expression of microRNAs plays vital roles in tumor development and progression. As transcription factors (TFs) are the critical components of signaling cascades, specific targeting effects of microRNAs to specific TFs may determine the role of microRNAs in different cancers. In this...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics