title: Knockdown of contactin-1 expression suppresses invasion and metastasis of lung adenocarcinoma.
abstract: 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.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Ching-Yao
authors.initials: CY
authors.lastname: Yang
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.forename: Lin-Hung
authors.initials: LH
authors.lastname: Wei
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Ming-Yang
authors.initials: MY
authors.lastname: Wang
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: 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
chemical_list: 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