Cooperation of protease-activated receptor 1 and integrin ανβ5 in thrombin-mediated             lung cancer cell invasion.
Protease-activated receptor 1 (PAR1) and integrins play an important role             in thrombin-mediated tumor cell invasion. However, the role of PAR1 and integrin             ανβ5 and the relationship between the two receptors in thrombin-induced lung cancer             invasion remains unknown. Moreover, the mechanisms through which immobilized thrombin             facilitates tumor invasion are poorly understood. In this study, both native and             immobilized thrombin promoted lung cancer cell adhesion, migration and extracellular             signal-regulated kinase phosphorylation. Integrin ανβ5 is involved in both native             and immobilized thrombin-mediated tumor cell invasion; PAR1 had no effect on immobilized             thrombin-mediated cell invasion. PAR1 and integrin ανβ5 colocalized on the surface             of native thrombin-treated cells. This study suggests that targeting of integrin             ανβ5 or the PAR1-integrin ανβ5 complex may present an important therapeutic opportunity             to prevent lung cancer invasion.
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
Lingyun
L
Zhu
Xiudong
X
Wang
Jie
J
Wu
Dekui
D
Mao
Zhishan
Z
Xu
Ziyang
Z
He
Aiping
A
Yu
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology*
D055767:Immobilized Proteins; D044463:Receptor, PAR-1; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D013917:Thrombin