delta-Catenin promotes malignant phenotype of non-small cell lung cancer by non-competitive binding to E-cadherin with p120ctn in cytoplasm.
As a member of the catenin family, little is known about the clinical significance and possible mechanism of delta-catenin expression in numerous tumours. We examined the expression of delta-catenin by immunohistochemistry in 115 cases of non-small cell lung cancer (NSCLC) (including 65 cases with follow-up records and 50 cases with paired lymph node metastasis lesions). The mRNA and protein expression of delta-catenin was also detected in 30 cases of paired lung cancer tissues and normal lung tissues by RT-PCR and western blotting, respectively. Co-immunoprecipitation was used to examine whether delta-catenin competitively bound to E-cadherin with p120ctn in lung cancer cells or not. The effects of delta-catenin on the activity of small GTPases and the biological behaviour of lung cancer cells were explored by pull-down assay, flow cytometry, MTT, and Matrigel invasive assay. The results showed that the mRNA and protein expression of delta-catenin was increased in lung cancer tissues; the positive expression rate of delta-catenin was significantly increased in adenocarcinoma, stage III-IV, paired lymph node metastasis lesions, and primary tumours with lymph node metastasis (all p < 0.05); and the postoperative survival period of patients with delta-catenin-positive expression was shorter than that of patients with delta-catenin-negative expression (p < 0.05). No competition between delta-catenin and p120ctn for binding to E-cadherin in cytoplasm was found in two lung cancer cell lines. By regulating the activity of small GTPases and changing the cell cycle, delta-catenin could promote the proliferation and invasion of lung cancer cells. We conclude that delta-catenin is an oncoprotein overexpressed in NSCLC and that increased delta-catenin expression is critical for maintenance of the malignant phenotype of lung cancer.
Zhang
Jun-Yi
JY
Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, China.
Wang
Yan
Y
Zhang
Di
D
Yang
Zhi-Qiang
ZQ
Dong
Xin-Jun
XJ
Jiang
Gui-Yang
GY
Zhang
Peng-Xin
PX
Dai
Shun-Dong
SD
Dong
Qian-Ze
QZ
Han
Yang
Y
Zhang
Sheng
S
Cui
Quan-Zhe
QZ
Wang
En-Hua
EH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D051177:Catenins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D003094:Collagen; D003593:Cytoplasm / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007797:Laminin; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D000095002:Delta Catenin
D014408:Biomarkers, Tumor; D015820:Cadherins; D051177:Catenins; D004338:Drug Combinations; D007797:Laminin; D009363:Neoplasm Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D000095002:Delta Catenin; C000722347:CTNND1 protein, human