Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma.
Numerous genetic changes are associated with cancer cell metastasis and invasion. In search for key regulators of invasion and metastasis, a panel of lung cancer cell lines with different invasive ability was screened. The gene for contactin-1 was found to play an essential role in tumor invasion and metastasis. Suppression of contactin-1 expression abolished the ability of lung adenocarcinoma cells to invade Matrigel in vitro as well as the polymerization of filamentous-actin and the formation of focal adhesion structures. Furthermore, knockdown of contactin-1 resulted in extensive inhibition of tumor metastasis and in increased survival in an animal model. RhoA but not Cdc42 or Rac1 was found to serve a critical role in contactin-1-mediated invasion and metastasis. Contactin-1-specific RNA interference resulted in loss of metastatic and invasive capacity in both in vitro and in vivo models. This loss was overturned by constitutive expression of the active form of RhoA. Contactin-1 was differentially expressed in tumor tissues, and its expression correlated with tumor stage, lymph node metastasis, and patient survival. Contactin-1 is proposed to function importantly in the invasion and metastasis of lung adenocarcinoma cells via RhoA-mediated mechanisms.
Su
Jen-Liang
JL
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yang
Ching-Yao
CY
Shih
Jin-Yuan
JY
Wei
Lin-Hung
LH
Hsieh
Chang-Yao
CY
Jeng
Yung-Ming
YM
Wang
Ming-Yang
MY
Yang
Pan-Chyr
PC
Kuo
Min-Liang
ML
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D058967:Contactin 1; D058966:Contactins; D022001:Focal Adhesions / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D014407:Tumor Cells, Cultured; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; C548669:CNTN1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D058966:Contactins; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein