Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24570268
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Nuclear localization of Kaiso promotes the poorly differentiated phenotype and
EMT in infiltrating ductal carcinomas
#MMPMID24570268
Jones J
; Wang H
; Karanam B
; Theodore S
; Dean-Colomb W
; Welch DR
; Grizzle W
; Yates C
Clin Exp Metastasis
2014[Jun]; 31
(5
): 497-510
PMID24570268
show ga
The expression and biological consequences of Kaiso, a novel bi-modal
transcription factor, in infiltrating ductal carcinomas (IDCs) have not been
widely investigated. In the present study, we determined Kaiso expression and
subcellular localization in 146 normal tissues, 376 IDCs, and 85 lymph node
metastases. In IDCs, there was higher Kaiso expression in both the cytoplasmic
and nuclear compartments, which correlated with age <48 (cytoplasmic p < 0.0093;
nuclear p < 0.0001) and moderate differentiation (cytoplasmic p < 0.0042; nuclear
p < 0.0001), as determined by Chi square analysis. However, only nuclear Kaiso
correlated with poor prognostic factors, i.e., race (African Americans) (p <
0.0001), poor differentiation (p < 0.0001), and metastases (p < 0.0001). Nuclear
Kaiso was also associated with worse overall survival (p < 0.0019), with African
American patients displaying worse survival rates relative to Caucasian patients
(p < 0.029). MCF-7 (non-metastatic), MDA-MB-468 (few metastases), and MDA-MB-231
(highly metastatic) breast cancer cells demonstrated increasing Kaiso levels,
with more nuclear localization in the highly metastatic cell line.
Over-expression of Kaiso in MCF-7 cells increased cell migration and invasion,
but treatment of MDA-MB-468 and MDA-MB-231 cells with si-Kaiso decreased cell
migration and invasion and induced expression of E-cadherin RNA and protein.
E-cadherin re-expression was associated with a reversal of mesenchymal associated
cadherins, N-cadherin and cadherin 11, as well as decreased vitamin expression.
Further, Kaiso directly bound to methylated sequences in the E-cadherin promoter,
an effect prevented by 5-aza-2-deoxycytidine. Immunofluorescence co-staining of
poorly differentiated IDCs demonstrated that nuclear Kaiso is associated with a
loss of E-cadherin expression. These findings support a role for Kaiso in
promoting aggressive breast tumors.
free
free
free
