Abstract

This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Epithelial-mesenchymal transition (EMT) occurs during normal embryonic development and epithelial tumor progression. Several factors associated with EMT contribute to motility, invasion, and angiogenesis, and may be important therapeutic targets for prostate cancer metastasis. Understanding the factors that contribute to EMT and prostate cancer metastasis is crucial for development of cancer therapies. For example, Snail transcription factor has been identified as an important factor that can induce EMT in breast and colon cancer. However, the role of EMT in prostate cancer is not well defined and good EMT models are lacking. Recently we have established an EMT model for prostate cancer progression using the ARCaP cell model overexpressing Snail. The goal of this proposal is to study the role of Snail transcription factor in prostate cancer progression and metastasis. We have found that Snail-induced EMT in prostate cancer cells involves reactive oxygen species (ROS) and receptor activator of NFkB (RANKL), two factors that are important in cancer disease progression and bone metastatic lesions, respectively. This proposal will elucidate the biological significance of Snail, with emphasis of its role in prostate cancer bone metastasis. In addition, we will characterize the signaling pathway of Snail-induced EMT, and finally examine the effect of antagonizing Snail expression on tumor aggressiveness in vitro and in vivo. We believe these studies will identify Snail as an attractive therapeutic target not only for EMT during primary tumor progression but also for bone metastatic lesions at the secondary site.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
2G12RR003062-22
Application #
7715357
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2008-09-01
Project End
2009-06-30
Budget Start
2008-09-01
Budget End
2009-06-30
Support Year
22
Fiscal Year
2008
Total Cost
$215,497
Indirect Cost

  Institution

Name
Clark Atlanta University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
065325177
City
Atlanta
State
GA
Country
United States
Zip Code
30314

  Publications

Morton, Derrick J; Patel, Divya; Joshi, Jugal et al. (2017) ID4 regulates transcriptional activity of wild type and mutant p53 via K373 acetylation. Oncotarget 8:2536-2549
Joshi, Jugal Bharat; Patel, Divya; Morton, Derrick J et al. (2017) Inactivation of ID4 promotes a CRPC phenotype with constitutive AR activation through FKBP52. Mol Oncol 11:337-357
Komaragiri, Shravan Kumar; Bostanthirige, Dhanushka H; Morton, Derrick J et al. (2016) ID4 promotes AR expression and blocks tumorigenicity of PC3 prostate cancer cells. Biochem Biophys Res Commun 478:60-66
Wilder, Catera L; Walton, Charlene; Watson, Valencia et al. (2016) Differential cathepsin responses to inhibitor-induced feedback: E-64 and cystatin C elevate active cathepsin S and suppress active cathepsin L in breast cancer cells. Int J Biochem Cell Biol 79:199-208
Burton, Liza J; Smith, Basil A; Smith, Bethany N et al. (2015) Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells. Carcinogenesis 36:1019-27
Goodson 3rd, William H; Lowe, Leroy; Carpenter, David O et al. (2015) Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis 36 Suppl 1:S254-96
Brown, Shanora G; Knowell, Ashley E; Hunt, Aisha et al. (2015) Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis. Prostate 75:266-79
Muniyan, Sakthivel; Chou, Yu-Wei; Tsai, Te-Jung et al. (2015) p66Shc longevity protein regulates the proliferation of human ovarian cancer cells. Mol Carcinog 54:618-31
Chinaranagari, Swathi; Sharma, Pankaj; Bowen, Nathan J et al. (2015) Prostate cancer epigenome. Methods Mol Biol 1238:125-40
Mandal, S; Abebe, F; Chaudhary, J (2014) -174G/C polymorphism in the interleukin-6 promoter is differently associated with prostate cancer incidence depending on race. Genet Mol Res 13:139-51

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