P120-catenin isoforms 1A and 3A differently affect invasion and proliferation of lung cancer cells.
Different isoforms of p120-catenin (p120ctn), a member of the Armadillo gene family, are variably expressed in different tissues as a result of alternative splicing and the use of multiple translation initiation codons. When expressed in cancer cells, these isoforms may confer different properties with respect to cell adhesion and invasion. We have previously reported that the p120ctn isoforms 1 and 3 were the most highly expressed isoforms in normal lung tissues, and their expression level was reduced in lung tumor cells. To precisely define their biological roles, we transfected p120ctn isoforms 1A and 3A into the lung cancer cell lines A549 and NCI-H460. Enhanced expression of p120ctn isoform 1A not only upregulated E-cadherin and beta-catenin, but also downregulated the Rac1 activity, and as a result, inhibited the ability of cells to invade. In contrast, overexpression of p120ctn isoform 3A led to the inactivation of Cdc42 and the activation of RhoA, and had a smaller influence on invasion. However, we found that isoform 3A had a greater ability than isoform 1A in both inhibiting the cell cycle and reducing tumor cell proliferation. The present study revealed that p120ctn isoforms 1A and 3A differently regulated the adhesive, proliferative, and invasive properties of lung cancer cells through distinct mechanisms.
Liu
Yang
Y
Department of Pathology, College of Basic Medical Sciences, China Medical University and Department of Pathology, First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Dong
Qian-Ze
QZ
Zhao
Yue
Y
Dong
Xin-Jun
XJ
Miao
Yuan
Y
Dai
Shun-Dong
SD
Yang
Zhi-Qiang
ZQ
Zhang
Di
D
Wang
Yan
Y
Li
Qing-Chang
QC
Zhao
Chen
C
Wang
En-Hua
EH
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D051177:Catenins; D002448:Cell Adhesion / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000095002:Delta Catenin
D051177:Catenins; D015815:Cell Adhesion Molecules; D010750:Phosphoproteins; D020033:Protein Isoforms; D000095002:Delta Catenin