Upregulation of δ-catenin is associated with poor prognosis and enhances transcriptional activity through Kaiso in non-small-cell lung cancer.
δ-Catenin is the only member of the p120 catenin (p120ctn) subfamily that its primary expression is restricted to the brain. Since δ-catenin is upregulated in human lung cancer, the effects of δ-catenin overexpression in lung cancer still need to be clarified. Immunohistochemistry was performed to investigate the expression of δ-catenin and Kaiso, a δ-catenin-binding transcription factor, in 151 lung cancer specimens. A correlation between cytoplasmic δ-catenin and Kaiso expression was also associated with high TNM stage, lymph node metastases and poor prognosis. Co-immunoprecipitation assay confirmed the interactions of δ-catenin and Kaiso in lung cancer cells. In addition, gene transfection and RNAi technology were used to demonstrate that increased δ-catenin expression was promoted, whereas its knockdown suppressed its lung cancer invasive ability. In addition, methylation-specific PCR and ChIP assay demonstrated that δ-catenin could regulate MTA2 via Kaiso in a methylation-dependent manner, while it could regulate cyclin D1 and MMP7 expression through Kaiso in a sequence-specific manner. In conclusion, a δ-catenin/Kaiso pathway exists in lung cancer cells. Increased δ-catenin expression is critical for maintenance of the malignant phenotype of lung cancer, making δ-catenin a candidate target protein for future cancer therapeutics.
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Shun-Dong
SD
Dai
Yan
Y
Wang
Jun-Yi
JY
Zhang
Di
D
Zhang
Peng-Xin
PX
Zhang
Gui-Yang
GY
Jiang
Yan
Y
Han
Sheng
S
Zhang
Quan-Zhe
QZ
Cui
En-Hua
EH
Wang
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D051177:Catenins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics; D005260:Female; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D015854:Up-Regulation; D000095002:Delta Catenin
C530104:CCND1 protein, human; D051177:Catenins; D012097:Repressor Proteins; D014157:Transcription Factors; C492254:ZBTB33 protein, human; D019938:Cyclin D1; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C120917:MTA2 protein, human; D006655:Histone Deacetylases; D000095002:Delta Catenin; C000722347:CTNND1 protein, human