Ablation of p120-catenin enhances invasion and metastasis of human lung cancer cells.
p120-catenin, a member of the Armadillo gene family, has emerged as both a master regulator of cadherin stability and an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis. We have reported previously that abnormal expression of p120-catenin is associated with lymph node metastasis in lung squamous cell carcinomas (SCC) and adenocarcinomas. To investigate the role and possible mechanism of p120-catenin in lung cancer, we knocked down p120-catenin using small interfering RNA (siRNA). We found that ablation of p120-catenin reduced the levels of E-cadherin and beta-catenin proteins, as well as the mRNA of beta-catenin. Furthermore, p120-catenin depletion inactivated RhoA, but increased the activity of Cdc42 and Rac1, and promoted proliferation and the invasive ability of lung cancer cells both in vitro and in vivo. Our data reveal that p120-catenin gene knockdown enhances the metastasis of lung cancer cells, probably by either depressing cell-cell adhesion due to lower levels of E-cadherin and beta-catenin, or altering the activity of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.
Liu
Yang
Y
Department of Pathology, College of Basic Medical Sciences, China Medical University, Heping District, Shenyang City, Liaoning Province, China.
Li
Qing-Chang
QC
Miao
Yuan
Y
Xu
Hong-Tao
HT
Dai
Shun-Dong
SD
Wei
Qiang
Q
Dong
Qian-Ze
QZ
Dong
Xin-Jun
XJ
Zhao
Yue
Y
Zhao
Chen
C
Wang
En-Hua
EH
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D051176:beta Catenin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D051176:beta Catenin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin; C000722347:CTNND1 protein, human