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Nuclear Kaiso Indicates Aggressive Prostate Cancers and Promotes Migration and Invasiveness of Prostate Cancer Cells.
Jacqueline Jones,* Honghe Wang,* Jianjun Zhou,* Shana Hardy,* Timothy Turner,* David Austin,* Qinghua He,† Alan Wells,‡ William E. Grizzle,§
and Clayton Yates*
From the Department of Biology,* Center for Cancer Research, and the Department of Chemical Engineering,† Tuskegee University, Tuskegee, Alabama; the Department of Pathology, Pittsburgh Veterans Affairs Medical Center, and the Department of Pathology,‡ University of Pittsburgh, Pittsburgh, Pennsylvania; and the Department of Pathology,§ University of Alabama at Birmingham School of Medicine, Birmingham, Alabama
The American Journal of Pathology, Volume 181, Issue 5 , Pages 1836-1846, November 2012, DOI:10.1016/j.ajpath.2012.08.008
"Nuclear Kaiso Indicates Aggressive Prostate Cancers and Promotes Migration and Invasiveness of Prostate Cancer Cells," submitted by Jones et al, reports that nuclear expression of Kaiso correlates with clinically advanced characteristics of prostate cancer, especially in African American men. Utilizing multiple cell culture models that mimic a similar phenomenon found in human prostate tissue, we were able to determine that epidermal growth factor (EGF) receptor up-regulates Kaiso at the RNA and protein levels in prostate cancer cell lines, but more interestingly causes a shift of cytoplasmic Kaiso to the nucleus that is reversed by the EGF receptor-specific kinase inhibitor, PD153035. Inhibition of Kaiso in the multiple cell culture models results in decreases in cell migration and invasion even in the presence of EGF, while simultaneously causing increases in E-cadherin expression, as well as a reversal of EMT-related proteins and cell morphology. Moreover, Kaiso was found to regulate E-cadherin expression directly by binding to methylated regions in the promoter. Our findings establish a defined oncogenic role of Kaiso, a bimodal transcription factor, to regulate gene expression epigenetically and promote the progression of prostate cancer.