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Kaiso: A Key Regulator in EMT and Cancer Progression
Author(s) -
Jones Jacqueline Denise,
Wang Honghe,
He Peter,
Grizzle William,
Turner Timothy,
Yates Clayton
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.142.6
Subject(s) - cancer research , metastasis , dna methylation , downregulation and upregulation , breast cancer , cancer , tumor progression , metastatic breast cancer , biology , gene expression , medicine , gene , biochemistry
Advanced stages of cancer are characterized by increased aggressiveness, invasiveness, and the downregulation of tumor suppressor genes via methylation. Kaiso, a bi‐modal transcription factor, interacts with DNA through either a DNA consensus sequence or methylated CpG di nucleotides thus regulating gene expression. A clinical role for Kaiso expression in advanced stages of breast cancer remains unclear. Here we investigate the ability of kaiso to decrease the metastatic functional characteristics of breast cancer progression. Immunohistochemistry was performed to examine protein expression and localization in human breast tissue. siRNA kaiso treated cells were used to assess cell motility and invasion. An overall increase in Kaiso expression was found in primary tumor samples and this increased as cancer progressed to distant sites. Additionally, nuclear localization of Kaiso was observed in primary tumor and lymph node metastasis in breast tumors. Construct treated cell lines showed a delay in cell motility, invasion. 5‐aza‐2′‐deoxycytidine treated cells showed a re‐expression of tumor suppressor E‐cadherin, which correlated with E‐cadherin re‐expression in siRNA Kaiso treated cells. Downregulation of E‐cadherin, migration and invasion are key to cancer progression and metastasis. Our results reveal kaiso as a potential indicator and/or therapeutic agent of breast cancer metastasis.