title: Nuclear Kaiso indicates aggressive prostate cancers and promotes migration and invasiveness of prostate cancer cells.
abstract: Kaiso, a p120 catenin-binding protein, is expressed in the cytoplasmic and nuclear compartments of cells; however, the biological consequences and clinical implications of a shift between these compartments have yet to be established. Herein, we report an enrichment of nuclear Kaiso expression in cells of primary and metastatic prostate tumors relative to the normal prostate epithelium. Nuclear expression of Kaiso correlates with Gleason score (P < 0.001) and tumor grade (P < 0.001). There is higher nuclear expression of Kaiso in primary tumor/normal matched samples and in primary tumors from African American men (P < 0.0001). We further found 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. In both DU-145 and PC-3 prostate cancer cell lines, Kaiso inhibition (short hairpin RNA-Kaiso) decreased cell migration and invasion even in the presence of EGF. Further, Kaiso directly binds to the E-cadherin promoter, and inhibition of Kaiso in PC-3 cells results in increased E-cadherin expression, as well as re-establishment of cell-cell contacts. In addition, Kaiso-depleted cells show more epithelial morphology and a reversal of the mesenchymal markers N-cadherin and fibronectin. Our findings establish a defined oncogenic role of Kaiso in promoting the progression of prostate cancer.
authors.affiliation: Department of Biology, Center for Cancer Research, Tuskegee University, Alabama, USA.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Jones
authors.forename: Honghe
authors.initials: H
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhou
authors.forename: Shana
authors.initials: S
authors.lastname: Hardy
authors.forename: Timothy
authors.initials: T
authors.lastname: Turner
authors.forename: David
authors.initials: D
authors.lastname: Austin
authors.forename: Qinghua
authors.initials: Q
authors.lastname: He
authors.forename: Alan
authors.initials: A
authors.lastname: Wells
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.forename: Clayton
authors.initials: C
authors.lastname: Yates
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D014157:Transcription Factors; C492254:ZBTB33 protein, human; D004815:Epidermal Growth Factor; D066246:ErbB Receptors